Biology subjects

Wei, L.

Publications and source records attributed to Wei, L..

At least 145 records · Page 8Linked to original sources

bioRxiv2021

A G-lectin Receptor Kinase is a Negative Regulator of Arabidopsis Immunity Against Root-Knot Nematode Meloidogyne incognita

Root-knot nematodes (Meloidogyne spp., RKN) are responsible for extensive crop losses worldwide. For infection, they penetrate plant roots, migrate between plant cells, and establish feeding sites, known as giant cells, in the root pericycle. Previously, we found that nematode perception and early plant responses were similar to those for microbial pathogens and require the BAK1 co-receptor in Arabidopsis thaliana and tomato. To identify additional receptors involved in this process, we implemented a reverse genetic screen for resistance or sensitivity to RKN using Arabidopsis T-DNA alleles of genes encoding transmembrane receptor-like kinases. This screen identified a pair of allelic mutations with enhanced resistance to RKN in a gene we named ENHANCED RESISTANCE TO NEMATODES 1 (ERN1). ERN1 encodes a G-type lectin receptor kinase (G-LecRK) with a single pass transmembrane domain. Further characterization showed that ern1 mutants displayed stronger activation of MAP kinases, elevated levels of the defense marker MYB51, and enhanced H202 accumulation in roots upon RKN elicitor treatments. Elevated MYB51 expression and ROS burst were also observed in leaves of ern1 mutants upon flg22 treatment. Complementation of ern1.1 with 35S- or native promotor-driven ERN1 rescued the RKN infection and enhanced defense phenotypes. Taken together, our results indicate that ERN1 is an important negative regulator of immunity. One sentence summaryA plasma membrane localized G-lectin receptor kinase acts as a negative immune regulator by interfering with defense responses activated by nematode and microbial elicitors.

plant biology↗

bioRxiv2021

The northern gene flow into southeastern East Asians inferred from genome-wide array genotyping

The population history of Southeast China remains poorly understood due to the sparse sampling of present-day populations and far less modeling with ancient genomic data. We here newly reported genome-wide genotyping data from 207 present-day Han Chinese and Hmong-Mien-speaking She people from Fujian and Taiwan, southeast China. We co-analyzed with 66 early-Neolithic to Iron-Age ancient Fujian and Taiwan individuals obtained from literature to explore the genetic continuity and admixture based on the genetic variations of high-resolution time transect. We found the genetic differentiation between northern and southern East Asians defined by a north-south East Asian genetic cline and the studied southern East Asians were clustered in the southern end of this cline. We also found that southeastern coastal continental modern East Asians harbored the genetic differentiation with other southern Tai-Kadai, Hmong-Mien, Austronesian and Austroasiatic speakers, as well as geographically close Neolithic-to-Iron Age populations, but relatedly close to post-Neolithic Yellow River ancients, which suggested the influence of southward gene flow on the modern southern coastal gene pool. Besides, we also identified one new Hmong-Mien genetic cline in East Asia with the coastal Fujian She localizing at the intersection position between Hmong-Mien and Han clines in the principal component analysis. She people show stronger genetic affinity with southern East Asian indigenous populations with the main ancestry deriving from Hanben-related populations. The southeastern Han Chinese could be modeled with the primary ancestry deriving from the group related to the Yellow River Basin millet farmers and the remaining from groups related to southeastern ancient indigenous rice farmers, which was consistent with the northern China origin of modern southeastern Han Chinese and in line with the historically and archaeologically attested southward migrations of Han people and their ancestors. Interestingly, f4-statistics and three-way admixture model results showed both coastal ancient sources related to Austronesian speakers and inland ancient sources related to Austroasiatic speakers complexed the modern observed fine-scale genetic structure here. Our estimated north-south admixture time ranges based on the decay of the linkage disequilibrium spanned from the Bronze age to historic periods, suggesting the recent large-scale population migrations and subsequent admixture participated in the formation of modern Han in Southeast Asia.

genetics↗

bioRxiv2021

A human ensemble cell atlas (hECA) enables in data cell sorting

Single-cell omics data can characterize multifaceted features of massive cells and bring significant insights to biomedical researches. The accumulation of single-cell data provides growing resources for constructing atlases for all cells of a human organ or the whole body. The true assembly of a cell atlas should be cell-centric rather than file-centric. We proposed a unified information framework enabling seamless cell-centric data assembly and developed a human Ensemble Cell Atlas (hECA) as an instance. hECA version 1.0 assembled scRNA-seq data across multiple studies into one orchestrated data repository. It contains 1,093,299 labeled cells and metadata from 116 published human single-cell studies, covering 38 human organs and 11 systems. We invented three methods of applications based on the cell-centric assembly: "In data" cell sorting enables targeted data retrieval in the full atlas with customizable logic expressions; The "quantitative portraiture" system provides a multi-view presentation of biological entities (organs, cell types, and genes) of multiple granularities; The customizable reference creation allows users to use the cell-centric assembly to generate references for their own cell type annotations. Case studies on agile construction of user-defined sub-atlases and "in data" investigation of CAR-T off-targets in multiple organs showed the great potential of cell-centric atlas assembly.

bioinformatics↗

bioRxiv2021

Genomic insights into the differentiated population admixture structure and demographic history of North East Asians

North China and South Siberia, mainly populated by Altaic-speaking populations, possess extensive ethnolinguistic diversity and serve as the crossroad for the initial peopling of America and western-eastern trans-continental communication. Yet, the complex scenarios of genetic origin, population structure, and admixture history of North-East Asia remain to be fully characterized, especially for Mongolic people in China with a genome-wide perspective. Thus, we genotyped genome-wide SNPs for 510 individuals from 38 Chinese Mongolic, Tungusic, and Sinitic populations to explore the sharing alleles and haplotypes within the studied groups and following merged it with 3508 modern and ancient Eurasian individuals to reconstruct the deep evolutionary and natural selection history of northern East Asians. We identified significant substructures within Altaic-speaking populations with the primary common ancestry linked to the Neolithic northern East Asians: Western Turkic people harbored more western Eurasian ancestry; Northern Mongolic people in Siberia and eastern Tungusic people in Amur River Basin (ARB) possessed dominant Neolithic Mongolian Plateau (MP) or ARB ancestry; Southern Mongolic people in China owned obvious genetic impact from Neolithic Yellow River Basin (YRB) farmers. Additionally, we found the differentiated admixture history between western and eastern Mongolians and geographically close Northeast Hans: the former received a genetic impact from western Eurasians and the latter retained the dominant YRB and ARB Neolithic ancestry. Moreover, we demonstrated that Kalmyk people from the northern Caucasus Mountain possessed a strong genetic affinity with Neolithic MP people, supporting the hypothesis of their eastern Eurasian origin and long-distance migration history. We also illuminated that historic pastoral empires in the MP contributed considerably to the gene pool of northern Mongolic people but rarely to southern ones. We finally found natural signatures in Mongolians associated with alcohol metabolism. Generally, our results not only illuminated that complex population migration and admixture of Neolithic ancestral sources from the MP or ARB played an important role in the spread of Altaic-speaking populations and Proto-Altaic language, which partly supported the Northeast Asia-origin hypothesis, but also demonstrated that the observed multi-sources of genetic diversity contributed significantly to the modern existing extensive ethnolinguistic diversity in North-East Asia.

genomics↗

bioRxiv2021

A Deep Learning Framework for Prediction of Clinical Drug Response of Cancer Patients and Identification of Drug Sensitivity Biomarkers using Preclinical Samples

BackgroundPrediction of the response of cancer patients to different treatments and identification of biomarkers of drug sensitivity are two major goals of individualized medicine. In this study, we developed a deep learning framework called TINDL, completely trained on preclinical cancer cell lines, to predict the response of cancer patients to different treatments. TINDL utilizes a tissue-informed normalization to account for the tissue and cancer type of the tumours and to reduce the statistical discrepancies between cell lines and patient tumours. In addition, this model identifies a small set of genes whose mRNA expression are predictive of drug response in the trained model, enabling identification of biomarkers of drug sensitivity. ResultsUsing data from two large databases of cancer cell lines and cancer tumours, we showed that this model can distinguish between sensitive and resistant tumours for 10 (out of 14) drugs, outperforming various other machine learning models. In addition, our siRNA knockdown experiments on 10 genes identified by this model for one of the drugs (tamoxifen) confirmed that all of these genes significantly influence the drug sensitivity of the MCF7 cell line to this drug. In addition, genes implicated for multiple drugs pointed to shared mechanism of action among drugs and suggested several important signaling pathways. ConclusionsIn summary, this study provides a powerful deep learning framework for prediction of drug response and for identification of biomarkers of drug sensitivity in cancer.

bioinformatics↗

bioRxiv2021

ARIC: Accurate and robust inference of cell type proportions from bulk gene expression or DNA methylation data

Quantifying the cell proportions, especially for rare cell types in some scenarios, is of great value to track signals related to certain phenotypes or diseases. Although some methods have been pro-posed to infer cell proportions from multi-component bulk data, they are substantially less effective for estimating rare cell type proportions since they are highly sensitive against feature outliers and collinearity. Here we proposed a new deconvolution algorithm named ARIC to estimate cell type proportions from bulk gene expression or DNA methylation data. ARIC utilizes a novel two-step marker selection strategy, including component-wise condition number-based feature collinearity elimination and adaptive outlier markers removal. This strategy can systematically obtain effective markers that ensure a robust and precise weighted {upsilon}-support vector regression-based proportion prediction. We showed that ARIC can estimate fractions accurately in both DNA methylation and gene expression data from different experiments. Taken together, ARIC is a promising tool to solve the deconvolution problem of bulk data where rare components are of vital importance.

bioinformatics↗

bioRxiv2021

Emerging SARS-CoV-2 mutation hotspots associated with clinical outcomes

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the ongoing coronavirus disease 2019 (COVID-19) pandemic. Understanding the influence of mutations in the SARS-CoV-2 gene on clinical outcomes and related factors is critical for treatment and prevention. Here, we analyzed 209,551 high-coverage complete virus sequences and 321 RNA-seq samples to mine the mutations associated with clinical outcome in the SARS-CoV-2 genome. Several important hotspot variants were found to be associated with severe clinical outcomes. Q57H variant in ORF3a protein were found to be associated with higher mortality rate, and was high proportion in severe cases (39.36%) and 501Y.V2 strains (100%) but poorly proportional to asymptomatic cases (10.04%). T265I could change nsp2 structure and mitochondrial permeability, and evidently higher in severe cases (20.12%) and 501Y.V2 strains (100%) but lower in asymptomatic cases (1.43%). Additionally, R203K and G204R could decrease the flexibility and immunogenic property of N protein with high frequency among severe cases, VUI 202012/01 and 484K.V2 strains. Interestingly, the SARS-CoV-2 genome was more susceptible to mutation because of the high frequency of nt14408 mutation (which located in RNA polymerase) and the high expression levels of ADAR and APOBEC in severe clinical outcomes. In conclusion, several important mutation hotspots in the SARS-CoV-2 genome associated with clinical outcomes was found in our study, and that might correlate with different SARS-CoV-2 mortality rates.

bioinformatics↗

bioRxiv2021

Cinnamoyl-CoA Reductase 1 (CCR1) and CCR2 Function Divergently in Tissue Lignification, Flux Control and Cross-talk with Glucosinolate Pathway in Brassica napus

Cinnamoyl-CoA reductase (CCR) is the entry point of lignin pathway and a crucial locus in dissection and manipulation of associated traits, but its functional dissection in Brassicaceae plants is largely lagged behind though Arabidopsis thaliana CCR1 has been characterized to certain extent. Here, 16 CCR genes are identified from Brassica napus and its parental species B. rapa and B. oleracea. Brassicaceae CCR genes are divided into CCR1 subfamily and CCR2 subfamily with divergent organ-specificity, yellow-seed trait participation and stresses responsiveness. CCR1 is preferential in G- and H-lignins biosynthesis and vascular development, while CCR2 has a deviation to S-lignin biosynthesis and interfascicular fiber development. CCR1 has stronger effects on lignification-related development, lodging resistance, phenylpropanoid flux control and seed coat pigmentation, whereas CCR2 controls sinapates levels. CCR1 upregulation could delay bolting and flowering time, while CCR2 upregulation weakens vascular system in leaf due to suppressed G lignin accumulation. Besides, CCR1 and CCR2 are deeply but almost oppositely linked with glucosinolates metabolism through inter-pathway crosstalk. Strangely, upregulation of both CCR1 and CCR2 could not enhance resistance to UV-B and S. sclerotiorum though CCR2 is sharply induced by them. These results provide systemic dissection on Brassica CCRs and CCR1-CCR2 divergence in Brassicaceae. HighlightBrassicaceae contains two types of Cinnamoyl-CoA reductase. As revealed in Brassica napus, they are divergently involved in lignin monomer biosynthesis, tissue lignification, phenylpropanoid flux control, and inter-pathway crosstalk with glucosinolates.

plant biology↗

bioRxiv2021

NeuronMotif: Deciphering transcriptional cis-regulatory codes from deep neural networks

Discovering DNA regulatory sequence motifs and their relative positions are vital to understand the mechanisms of gene expression regulation. Such complicated motif grammars are difficult to be summarized from shallow models. Although Deep Convolutional Neural Network (DCNN) achieved great success in annotating cis-regulatory elements, few combinatorial motif grammars have been accurately interpreted due to the mixed signal in DCNN. To address this problem, we proposed NeuronMotif, a general backward decoupling algorithm, to reveal the homo-/hetero-typic motif combinations and arrangements embedded in convolutional neurons. We applied NeuronMotif on several widely-used DCNN models. Many uncovered motif grammars of deep convolutional neurons are supported by literature or ATAC-seq footprinting. We further diagnosed the sick neurons that are sensitive to adversarial noises, which can guide DCNN architecture optimization for better prediction performance and motif feature extraction. Overall, NeuronMotif enables decoding cis-regulatory codes from deep convolutional neurons and understanding DCNN from a novel perspective.

bioinformatics↗

bioRxiv2021

MMP12 Knockout Prevent Weight and Muscle Loss Induced by Cancer Cachexia

Weight loss and muscle wasting can have devastating impacts on survival and quality of life of patients with cancer cachexia. Here, we have established a hybrid mouse of ApcMin/+ mice and MMP12 knockout mice (ApcMin/+; MMP12-/-) and found that knockout MMP12 can suppress the weight and muscle loss of ApcMin/+ mice. In detail, we found that interleukin 6 was highly upregulated in the serum of cancer patients and MMP12 was increased in muscle of tumor-bearing mice. Interestingly, the interleukin 6 secreted by tumor cells led to MMP12 overexpression in the macrophages, which further resulted in degradation of insulin and insulin-like growth factor 1 and interruption of glycolipid metabolism. Notably, depletion of MMP12 prevented weight loss of ApcMin/+ mice. Our study uncovers the critical role of MMP12 in controlling weight and highlights the great potential of MMP12 in the treatment of cancer cachexia.

cancer biology↗

bioRxiv2021

Inhibition of HSP90 reversed STAT3 mediated muscle wasting induced by cancer cachexia

Cancer cachexia is one of the most common causes of death among cancer patients, no effective anti-cachectic treatment is currently available. In experimental cachectic models, aberrant activation of STAT3 in skeletal muscle has been found to contribute to muscle wasting. However, its clinical association, the factors regulating STAT3 activation, and the molecular mechanisms of STAT3-induced muscle atrophy in cancer cachexia remain incompletely understood. Here, we show that an enhanced interaction between STAT3 and HSP90, which causes the persistent STAT3 activation in the skeletal muscle of cancer cachexia patients, is the crucial event for the development of cachectic muscle wasting. Administration of HSP90 inhibitors alleviated the muscle wasting in C26 tumor-bearing cachetic mice model or C26 conditional medium induced C2C12 myotube atrophy. A mechanistic study indicated that in cachectic skeletal muscle, prolonged STAT3 activation triggered muscle wasting in a FOXO1-dependent manner, STAT3 activated FOXO1 by binding directly to its promoter. Our results provide key insights into the role of the HSP90/STAT3/FOXO1 axis in cachectic muscle wasting, which shows promising therapeutic potential as a target for the treatment of cancer cachexia.

pathology↗

bioRxiv2021

Small peptides modulate the immune function of the ion channel-like protein ACD6 in Arabidopsis thaliana

ACCELERATED CELL DEATH 6 (ACD6) mediates a trade-off between growth and defense in Arabidopsis thaliana. However, the precise biochemical mechanism by which ACD6 and related proteins in plants act remains enigmatic. Here, we identified two loci, MODULATOR OF HYPERACTIVE ACD6 1 (MHA1) and its paralog MHA1-LIKE (MHA1L), that code for [~]7 kDa proteins that differentially interact with specific ACD6 variants. MHA1L enhances accumulation of an ACD6 complex, thereby increasing activity of the ACD6 standard allele for regulating plant growth and defenses. ACD6 is a multipass transmembrane protein with intracellular ankyrin repeats that are structurally similar to those found in mammalian ion channels. Several lines of evidence link increased ACD6 activity to enhanced calcium influx, likely mediated by ACD6 itself and with MHA1L as a direct regulator of ACD6.

plant biology↗

bioRxiv2021

DISMIR: a deep learning-based cancer-detection method by integrating DNA sequence and methylation information of individual cell-free DNA reads

Detecting cancer signals in cell-free DNA (cfDNA) high-throughput sequencing data is emerging as a novel non-invasive cancer detection method. Due to the high cost of sequencing, it is crucial to make robust and precise prediction with low-depth cfDNA sequencing data. Here we propose a novel approach named DISMIR, which can provide ultrasensitive and robust cancer detection by integrating DNA sequence and methylation information in plasma cfDNA whole genome bisulfite sequencing (WGBS) data. DISMIR introduces a new feature termed as "switching region" to define cancer-specific differentially methylated regions, which can enrich the cancer-related signal at read-resolution. DISMIR applies a deep learning model to predict the source of every single read based on its DNA sequence and methylation state, and then predicts the risk that the plasma donor is suffering from cancer. DISMIR exhibited high accuracy and robustness on hepatocellular carcinoma detection by plasma cfDNA WGBS data even at ultra-low sequencing depths. Analysis showed that DISMIR tends to be insensitive to alterations of single CpG sites methylation states, which suggests DISMIR could resist to technical noise of WGBS. All these results showed DISMIR with the potential to be a precise and robust method for low-cost early cancer detection.

bioinformatics↗

bioRxiv2021

Super-Resolution Label-free Volumetric Vibrational Imaging

Innovations in high-resolution optical imaging have allowed visualization of nanoscale biological structures and connections. However, super-resolution fluorescence techniques, including both optics-oriented and sample-expansion based, are limited in quantification and throughput especially in tissues from photobleaching or quenching of the fluorophores, and low-efficiency or non-uniform delivery of the probes. Here, we report a general sample-expansion vibrational imaging strategy, termed VISTA, for scalable label-free high-resolution interrogations of protein-rich biological structures with resolution down to 82 nm. VISTA achieves decent three-dimensional image quality through optimal retention of endogenous proteins, isotropic sample expansion, and deprivation of scattering lipids. Free from probe-labeling associated issues, VISTA offers unbiased and high-throughput tissue investigations. With correlative VISTA and immunofluorescence, we further validated the imaging specificity of VISTA and trained an image-segmentation model for label-free multi-component and volumetric prediction of nucleus, blood vessels, neuronal cells and dendrites in complex mouse brain tissues. VISTA could hence open new avenues for versatile biomedical studies.

neuroscience↗

bioRxiv2020

Dextran sulfate sodium salt corrupted colonic crypts declined the smooth muscle tension in mouse large intestine

Ulcerative colitis is one kind of colonic mucosa damage, shows high number of inflammatory epithelial cells. Dextran sulfate sodium salt (DSS) induce a milder onset of colitis or a more aggressive response. It may damage the protective effects on intestinal barrier. In this study, we investigated the damaging of colon crypts, evaluated the smooth muscle tension beneath corrupted crypts in DSS exposed mice. Methodsfemale specific-pathogen-free BALB/C mice (n=16) are randomly divided as: group A: control mice (n=4); group B: DSS-mice (colitis, 5% DSS in drink water, days 1 to 7, n = 12). The DSS is replaced every 2 days. On day 8, mice colons are excised from the colon-cecal junction to the anus. The distal colon segment is longitude incision and aberrant crypt area are determined by methylene blue staining method. The smooth muscle strip is separated and prepared for passive tension tests. The rest segment is fixed with 10% formalin and embedded in paraffin. Histological scores are evaluated in hematoxylin-eosin staining section: crypt damage (none = 0, basal 1/3 damaged = 1, basal 2/3 damaged = 2, only the surface epithelium is intact = 3, and entire crypt and epithelium are lost = 4). The smooth muscle passive tension beneath the aberrant crypt area in DSS-mice are tested and compared with the preparations from control mice. ResultsIn DSS uptake mice, the inflammation in large intestine mucosa damaged crypts with architectural distortions on day 7 (n=7). In crypts damage area, the smooth muscle passive tension and relative myogenic spontaneous contraction parameters are significantly reduced under the high preload conditions. The maximum rate of change of velocity of spontaneous contraction was noticeable attenuated. ConclusionOur findings demonstrate that low dosage DSS water drink result in corrupted colonic crypts. The corrupted crypts damage the large intestinal epithelium barrier, affect the smooth muscle functions, which declined in myogenic spontaneous contraction under the preload. This further may reduce the peristalsis in large intestine.

physiology↗

bioRxiv2020

The Establishment of Transgenerational Epigenetic Inheritance in the C. elegans Germline is Mediated by Lipid Metabolism

Environmental stress-induced epigenetic changes are inherited by germlines and profoundly affect the behavior and physiology of subsequent generations. However, the mechanisms by which acquired transgenerational epigenetic imprints are established in the parental germline remain poorly understood. In this study, we used Caenorhabditis elegans as a model system and demonstrated that a key node of metabolism-Pod-2, an acetyl-CoA carboxylase, together with vitellogenins (Vits), cholesterol-binding/transport proteins, guide establishment of the acquired transgenerational epigenetic modifications H3K27me3 in the parental germline. The loss of function of a Vit; its transporter or receptor; or its binding partner, pod-2, resulted in the loss of acquired epigenetic memory in the germline. Our findings indicate that lipid metabolism is a critical mediator for establishing transgenerational epigenetic imprints in the germline.

genetics↗

bioRxiv2020

Tissue-specific accumulation profiles of phorbol esters in Jatropha curcas and gene induction in response to abiotic and biotic stresses

Jatropha curcas L. (J. curcas), a shrub plant of the Euphorbiaceae family, has received enormous attention as a promising biofuel plant for the production of biodiesel and medical potential in ethnopharmacology. However, the tumor-promoter toxin phorbol esters present in J. curcas raises concerns for health and environmental risk as its large-scale cultivation limits the use of meal obtained after oil extraction for animal feed. Here, we determined the variation of phorbol ester profiles and contents in eight J. curcas tissues by high performance liquid chromatography (HPLC) and found phorbol esters present in all parts of the plant except the seed shell. We showed tissue-specific patterns of accumulation of phorbol esters and associated terpenoids at the transcriptomic level with high transcript levels in reproductive and young tissues. Genes involved in the same module of terpenoids biosynthesis were positively correlated. We further present diverse abiotic and biotic stresses that had different effects on the accumulation of transcripts in terpenoids shared and branched terpenoid pathways in plant seedlings. The fine-tuning of terpenoids biosynthesis may link with ecological functions in plants under extreme environments and defense against pathogens.

plant biology↗

bioRxiv2020

Overlapping activities of ELAV/Hu RNA binding proteins specify multiple neural alternative splicing programs

ELAV/Hu factors are conserved RNA binding proteins that play diverse roles in mRNA processing and regulation. The founding member, Drosophila Elav, was recognized as a vital neural factor 35 years ago. Nevertheless, still little is known about its impacts on the transcriptome, and potential functional overlap with its paralogs. Building on our recent findings that neural-specific lengthened 3 UTR isoforms are co-determined by ELAV/Hu factors, we address their impacts on splicing. In ectopic contexts, all three members (Elav, Fne and Rbp9) induce similar and broad changes to cassette exon and alternative last exon (ALE) splicing. Reciprocally, double mutants of elav/fne, but not elav alone, have opposite effects on both types of mRNA processing events in the larval CNS. Accordingly, while fne mutants are normal, fne loss strongly enhances elav mutants with respect to neuronal differentiation. While manipulation of Drosophila ELAV/Hu factors induces both exon skipping and inclusion, motif analysis indicates their major direct effects are to suppress cassette exon usage. Moreover, we find direct analogies in their roles in global promotion of distal ALE splicing and terminal 3 UTR extension, since both involve local suppression of proximal polyadenylation signals via ELAV/Hu binding sites downstream of cleavage sites. Finally, we provide evidence for analogous co-implementation of distal ALE and APA lengthening programs in mammalian neurons, linked to ELAV/Hu motifs downstream of regulated polyadenylation sites. Overall, ELAV/Hu proteins orchestrate multiple conserved programs of neuronal mRNA processing by suppressing alternative exons and polyadenylation sites.

molecular biology↗