Biology subjects

Luo, M.

Publications and source records attributed to Luo, M..

At least 37 records · Page 2Linked to original sources

bioRxiv2025

Host Microenvironment Reprogramming by Saccharides Overcomes Lung Barriers for mRNA Therapeutics

AbstractOvercoming biological barriers remains the paramount challenge for pulmonary mRNA therapeutics. Conventional approaches focus exclusively on passively optimizing formulation quality without controlling dynamic host barriers. Here, we pioneer a host-centric strategy by leveraging sugar that actively reprograms the airway microenvironment to boost IVT-mRNA transfection. Utilizing machine learning-accelerated screening of a chemically diverse saccharide library, we identify D-glucose as the best-performing candidate. Glucose assisted-delivery within lipid nanoparticles (Glu-LNP) achieves robust, lung-specific protein expression (up to 131.21-fold increase) across diverse preclinical models with reduced inflammation. In lung carcinoma models, Glu-LNP-encapsulated IL-12 mRNA reduced tumor burden by approximately 59.12% and improved survival by 2.5-fold compared to the LNP group. Mechanistically, glucose orchestrates a dual-pathway cascade: metabolic reprogramming via the Warburg effect elevates ATP, fueling endocytosis and translation; ATP further activates the P2Y2-IP3 signaling axis that triggers Ca2+ release and subsequent CLCA1/TMEM16A-dependent chloride/bicarbonate efflux, which remodels mucus barriers and enhances nanoparticle penetration. This bioenergetic and mucolytic host intervention strategy presents a broadly applicable paradigm to transcend delivery limitations for respiratory mRNA therapeutics.

bioengineering↗

bioRxiv2025

Ferret model of bleomycin-induced lung injury shares features of human idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a debilitating lung disease with limited therapeutic options. The development of effective therapies has been hindered by the lack of models that recapitulate key features of human disease. Here we report a bleomycin-induced ferret PF model characterized by an irreversible decrease in pulmonary compliance and an increase of opacification, accompanied by "honeycomb cyst-like" structures and "proximalization" of distal lung epithelium. Cellular and molecular analysis by single-nucleus RNA sequencing revealed a significant shift in distal lung epithelium towards proximal epithelial phenotype. Importantly, a histopathological pattern of bronchiolization encompassing divergent atypical epithelial cells and KRT17+/TP63+/KRT5low "basaloid-like" cells was present in the distal fibrotic lung lesions. Trajectory analysis revealed AT2 cells transition through multiple cell-states in bleomycin injured ferret lungs, particularly AT2 to KRT8high/KRT7low/SOX4+ and eventually to KRT8high/KRT7high/SFN+/TP63+/KRT5low "basaloid-like" cells. Further, immunofluorescence analyses demonstrated KRT7 and KRT8 populations reside overlaying the ACTA2-positive myofibroblasts in fibrotic foci, implying their pro-fibrogenic activity similar to human IPF lungs. Collectively, our results provide evidence that bleomycin-induced lung injury in ferrets recapitulates pathophysiological, cellular, and molecular features of human IPF, suggesting that they may be a reliable model for understanding mechanisms of IPF pathogenesis and for testing therapeutic strategies for treatment of IPF. Take Home MessageBleomycin-induced acute lung injury in the ferret recapitulates pathophysiological, cellular, and molecular features of human IPF; thus the ferret may be a reliable species for studying mechanisms of IPF pathogenesis and testing therapeutic strategies.

pathology↗

bioRxiv2025

Dual function of DOT1L suppresses tumor intrinsic immunogenicity in hepatocellular carcinoma

Immune checkpoint inhibitor (ICB) therapy for many cancers remains limited in patients overall response rate. Discovery and development of more effective combinatorial approaches is urgent. Here, through CRISPR/Cas9 genetic screens, we identify DOT1L as a versatile epigenetic factor that functions to suppress tumor-intrinsic immunity through a dual mechanism. Depletion of DOT1L induces the expression of transposable elements and subsequent type I interferon (IFN) response, and meanwhile lowers ZEB1 levels to further unleash the expression of immune-related genes. In turn, we demonstrate that DOT1L loss or treatment with the clinical stage inhibitor EPZ-5676 sensitizes tumors to ICB with increased immune infiltration in mice. More importantly, EPZ-5676 treatment alone is sufficient to enhance antitumor immunity in humanized mice. TCGA data analysis reveals an inverse correlation between DOT1L expression and IFN signatures across multiple cancer types. These findings provide a rationale for targeting DOT1L to improve tumor immunogenicity and overcome immunotherapy resistance. One Sentence SummaryCRISPR genetic screens identified DOT1L as a potential suppressor of tumor intrinsic immunogenicity

cell biology↗

bioRxiv2025

A biGWAS strategy reveals the genetic architecture of the interaction between wheat and Blumeria graminis f. sp. tritici

BackgroundWheat powdery mildew, caused by Blumeria graminis f. sp. tritici (Bgt) is one of the most significant diseases affecting global wheat production. Breeding for disease resistance (R) genes against Bgt often follows a boom-bust cycles, where cultivars with effective resistance are widely deployed on an expanding area until virulence emerges in the avirulence (Avr) pathogen population. While extensive effort has been devoted to identifying and cloning R genes, Avr genes remain relatively understudied, limiting our understanding of R-Avr interactions. That said, understanding R-Avr interactions is crucial for developing durable resistance strategies. ResultsWe conducted whole genome sequencing on 245 Bgt isolates collected from major wheat-growing regions in China, identifying 120 genetically unique isolates. Each of these unique isolates was inoculated and phenotyped on a diverse panel of wheat germplasm. Through Genome-Wide Association Analysis (GWAS) in both Bgt and wheat, we identified 65 Avr loci and 251 R loci overlapping with nine and eight cloned Avr or R genes, respectively. On average, each isolate carries eight Avr alleles, ranging from one to 17. Little geographical preference for Avr alleles or their combinations was observed, suggesting that disease resistance breeding against this pathogen should be coordinated at the national level. The level of resistance level is positively correlated with the number of R alleles carried by a wheat line, and the average frequency of an R allele is 2% among the wheat panel, indicating the potential for accumulating R alleles in breeding programs. We mapped 212 R-Avr interactions based on joint GWAS using both plant and pathogen genomes and cross-species epistasis, where a network of interactions was formed between wheat and Bgt. These interactions indicate that pyramiding five major R loci has the potential to confer resistance to half of the Avr loci. As a proof of concept, we successfully verified two previously described R-Avr pairs using tobacco experiments. Furthermore, we provided molecular validation evidence for three new Avr genes, including Bgt-50651, BgtE-5826 and BgtE-20009, and two new R-Avr interactions. Among them, Bgt-50651 interacts with Pm1a, Pm2a, and another unidentified R gene located near the Pm6/Pm52 interval. ConclusionOur study provides a framework for understanding the genetic interaction between plants and pathogens. The discovery of novel R/Avr loci and their complex interaction network underscores the need to integrate crop and pathogen genetic background, particularly the R/Avr allele composition, into breeding program design. These findings have significant implications for developing durable resistance strategies in wheat alongside offering valuable insights into the broader dynamics of plant-pathogen interactions.

genomics↗

bioRxiv2025

Multiple evolutionary events in host plant adaptation in Lepidoptera

The evolution of insect host adaptation is a key component of insect-plant coevolution, a complex process often shaped by multiple evolutionary events. In this study, we identified two UDP-glycosyltransferase (UGT) genes, SfruUGT33T10 and SfruUGT33F32, in the fall armyworm Spodoptera frugiperda, which play critical roles in the tolerance of benzoxazinoids (BXs), secondary metabolites in maize. These two detoxification enzymes exhibited distinct glycosylation patterns for BXs and varying detoxification efficiencies, reflecting independent evolutionary trajectories. Phylogenetic analyses revealed that SfruUGT33T10 originated independently within Noctuidae, while SfruUGT33F32 resulted from tandem duplication within the UGT33F gene family and may have undergone neofunctionalization within the Spodoptera genus. Our findings provide evidence that the evolution of these two UGT paralogs contributed to the variation in the tolerance to maize BXs among different Lepidopteran species. This research underscores the significance of multiple independent evolutionary routes in host plant adaptation and offer new insights into the complex evolutionary processes underlying insect-plant interactions.

evolutionary biology↗

bioRxiv2025

Characterization of two non-competing antibodies to influenza H3N2 hemagglutinin stem reveals its evolving antigenicity

The conserved stem domain of influenza hemagglutinin (HA), which is classified into group 1 and group 2, is a target of broadly neutralizing antibodies. While many group 1 HA stem antibodies have been described, much less is known about group 2 HA stem antibodies. This study structurally characterizes two group 2 HA stem antibodies, 2F02 and AG2-G02, targeting the central stem epitope and the lower stem epitope, respectively. Unlike prototypic group 2 HA stem antibodies, 2F02 and AG2-G02 do not compete for binding. Both antibodies offer protection in vivo despite having minimal neutralization activity in vitro. We further demonstrate that the natural evolution of HA2 position 32 restricts the binding of AG2-G02 to recent human H3N2 HAs and influences the binding of human plasma samples. Overall, these findings advance our understanding of the antigenicity of HA stem, which has important implications for the development of broadly protective influenza vaccines.

immunology↗

bioRxiv2025

Spatial distribution of the proteome in human body and cancers

A comprehensive spatial distribution of the proteome in human body and cancers is fundamental for understanding human biology and diseases including cancers. Here, we present an anatomically resolved human proteome derived from 1781 benign and malignant samples from 58 major tissue types encompassing 251 specific tissues and 25 carcinomas. Based on a spectral library covering over 75% of the human protein-coding genes with 208 understudied and 82 missing proteins characterized, we quantified over 13,000 proteins in these samples using data-independent acquisition proteomics. This data resource presents the so far most comprehensive quantitative proteomic landscape of human tissues and common carcinomas. It allows systematic evaluation of tissue-specific drug responses, identification of drug candidates that may be repurposed as antineoplastics, and discovery of novel targets for anticancer therapy. This resource, available as an online knowledgebase, refines our knowledge of spatial distribution of the human proteome and tumor-specific protein modulation.

systems biology↗

bioRxiv2025

The Interplay of Furin Cleavage and D614G in Modulating SARS-CoV-2 Spike Protein Dynamics

We report a detailed analysis of the full-length SARS-CoV-2 spike dynamics within a native-like membrane environment and variants inaccessible to studies on soluble constructs by conducting hydrogen-deuterium exchange mass spectrometry (HDX-MS) on enveloped virus-like particles (eVLPs) displaying various spike constructs. We find that the previously identified open-interface trimer conformation is sampled in all eVLP-displayed spike variants studied including sequences from engineered vaccine constructs and native viral sequences. The D614G mutation, which arose early in the pandemic, favors the canonical closed-interface prefusion conformation, potentially mitigating premature S1 shedding in the presence of a cleaved furin site and providing an evolutionary advantage to the virus. Remarkably, furin cleavage at the S1/S2 boundary allosterically increases the flexibility of the S2 site, which may facilitate increased TMPRSS2 processing, enhancing viral infectivity. The use of eVLPs in HDX-MS studies provides a powerful platform for studying viral and membrane proteins in near-native environments.

biophysics↗

bioRxiv2025

Modular DNA Barcoding of Nanobodies Enables Multiplexed in situ Protein Imaging and High-throughput Biomolecule Detection

Current immunodetection methods using antibody-DNA conjugates enable multiplexed target detection through orthogonal DNA barcodes, but existing conjugation approaches are labor-intensive and often compromise antibody function. Here we present a modular, site-specific, and cost-efficient DNA tagging strategy -- multiplexed and modular barcoding of antibodies (MaMBA). Utilizing nanobodies as modular adaptors, MaMBA enables direct site-specific labeling of off-the-shelf IgG antibodies with a one-component design. We first applied MaMBA to develop the misHCR method for highly multiplexed in situ protein imaging via orthogonal hybridization chain reaction (HCR). Its cleavable variant, misHCRn, achieves simultaneous visualization of 12 different targets within the same mouse brain sections through iterative probe use. We further extended the cleavable MaMBA to develop the barcode-linked immunosorbent assay (BLISA) for multiplexed and high-throughput biomolecule detections. By combining BLISA with next-generation sequencing, we successfully measured SARS-CoV-2 IgG and HBV-associated antigens in a large number of human serum samples. Additionally, we demonstrated a small-scale drug screen by using BLISA to simultaneously detect eight protein targets. In conclusion, MaMBA offers a highly modular and easily adaptable approach for antibody DNA-barcoding, which can be broadly applied in basic research and clinical diagnostics.

bioengineering↗

bioRxiv2024

Base-modified nucleotides mediate immune signaling in bacteria

Signaling from pathogen sensing to effector activation is a fundamental principle of cellular immunity. While cyclic (oligo)nucleotides have emerged as key signaling molecules, the existence of other messengers remains largely unexplored. Here, we reveal a bacterial anti-phage system that mediates immune signaling through nucleobase modification. Immunity is triggered by phage nucleotide kinases, which, combined with the system-encoded adenosine deaminase, produce deoxyinosine 5-triphosphate (dITP) as immune messengers. The dITP signal activates downstream effector to mediate cellular NAD+ depletion, resulting in population-level defense through the death of infected cells. To counteract immune signaling, phages deploy specialized enzymes that deplete cellular dAMP, the precursor of dITP messengers. Our findings uncover a nucleobase modification-based anti-phage signaling pathway, establishing noncanonical nucleotides as a new type of immune messengers in bacteria.

microbiology↗

bioRxiv2024

PRMT1-Mediated Metabolic Reprogramming Promotes Leukemogenesis

Copious expression of protein arginine methyltransferase 1 (PRMT1) is associated with poor survival in many types of cancers, including acute myeloid leukemia. We observed that a specific acute megakaryocytic leukemia (AMKL) cell line (6133) derived from RBM15-MKL1 knock-in mice exhibited heterogeneity in Prmt1 expression levels. Interestingly, only a subpopulation of 6133 cells expressing high levels of Prmt1 caused leukemia when transplanted into congenic mice. The PRMT1 inhibitor, MS023, effectively cured this PRMT1-driven leukemia. Seahorse analysis revealed that PRMT1 increased the extracellular acidification rate (ECAR) and decreased the oxygen consumption rate (OCR). Consistently, PRMT1 accelerated glucose consumption and led to the accumulation of lactic acid in the leukemia cells. The metabolomic analysis supported that PRMT1 stimulated the intracellular accumulation of lipids, which was further validated by FACS analysis with BODIPY 493/503. In line with fatty acid accumulation, PRMT1 downregulated the protein level of CPT1A, which is involved in the rate-limiting step of fatty acid oxidation. Furthermore, administering the glucose analogue 2-deoxy-glucose (2-DG) delayed AMKL progression and promoted cell differentiation. Ectopic expression of Cpt1a rescued the proliferation of 6133 cells ectopically expressing PRMT1 in the glucose-minus medium. In conclusion, PRMT1 upregulates glycolysis and downregulates fatty acid oxidation to enhance the proliferation capability of AMKL cells. Graphic Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=83 SRC="FIGDIR/small/628174v2_ufig1.gif" ALT="Figure 1"> View larger version (26K): org.highwire.dtl.DTLVardef@1ae96borg.highwire.dtl.DTLVardef@d27916org.highwire.dtl.DTLVardef@ba63corg.highwire.dtl.DTLVardef@cee9af_HPS_FORMAT_FIGEXP M_FIG C_FIG

cancer biology↗

bioRxiv2024

Targeted degradation of endogenous condensation-prone proteins improves crop performance

Effective methods, such as CRISPR and RNA interference, exist for modulating gene expression at DNA and RNA levels, but approaches for directly modifying endogenous proteins remain lacking in plants. Here, we develop a targeted condensation-prone-protein degradation (TCD) strategy to eliminate endogenous proteins, particularly those prone to condensation. We identify an E3 ligase, E3TCD1, that degrades itself but selectively targets other proteins when fused to them. In rice, transgenic E3TCD1 fusions with Teosinte branched 1 and Early flowering 3 (OsELF3) modulate tiller numbers and flowering times, respectively. The TCD system is also controllable. Using the ProTBF1-uORFsTBF1 expression control cassette, we can conditionally degrade the negative defense regulator OsELF3 upon pathogen invasion, enhancing rice resistance without interfering with rice flowering time. This method, unlike animal-targeting strategies, does not rely on small molecules, antibodies, or genetic knock-ins, showing promise as a gene therapeutic avenue for optimizing crop performance and potentially addressing human diseases.

plant biology↗

bioRxiv2024

An integrative layer-resolved atlas of the adult human meninges

The human meninges are a dynamic tri-layered brain border that plays a key role in brain development, CSF homeostasis, immune regulation, and higher-level brain function. The meninges have also been implicated in central nervous system (CNS) pathologies such as infection, autoimmunity, and brain trauma. To understand how the meningeal microenvironment is altered under pathological conditions it is necessary to have a complete understanding of its normotypic cellular architecture and function. To date, there is no complete atlas of the normotypic adult human meninges. By surgically extracting each human meningeal layer during surgery, we generated the first layer-resolved map of all meningeal cell types via an integration of whole cell single cell RNA sequencing, multiplexed error-robust fluorescence in situ hybridization (MERFISH), and protein immunolabelling. Since fibroblasts play key roles in meningeal homeostasis yet remain less well-characterised than other meningeal cell types, we deeply phenotyped these cells in all layers. We identified 10 fibroblast subpopulations with unique predicted functions that localise to distinct neuroanatomical niches. Fibroblast interaction analysis in the dura and subarachnoid space (SAS) uncovered novel interactions with vascular cell populations mediated by insulin growth factor signaling. Together, these data serve as a comprehensive resource for future investigations of meningeal function in the healthy and diseased brain.

neuroscience↗

bioRxiv2024

Airway applied IVT mRNA vaccine needs specific sequence design and high standard purification that removes devastating dsRNA contaminant

The development of next-generation mucosal mRNA vaccines is promising but extremely challenging. Major efforts have been focused on optimizing delivery systems, whereas it is still unknown whether the intrinsic quality of IVT mRNA significantly impacts the potency of airway inoculated mRNA vaccines. Here, we systematically demonstrate the mucosal mRNA vaccine requires a higher standard of purification and tailor-designed sequence to fulfil its potency compared to the parenteral route inoculated counterpart. We found double strand RNA (dsRNA) contaminants are prone to trigger innate immunoreaction in the airway that activates the mRNA degradation mechanism, thereby diminishing the mRNA expression and subsequent antigen-specific immune responses. To address these challenges, we developed a strategy that combines optimized untranslated regions (UTRs) screened from endogenous genes of pulmonary cells with affinity chromatography-based purification which removes almost all the dsRNA contaminants. The optimized mRNA administered via the airway route not only demonstrates superior protein expression (30-fold increase) and reduces inflammation in the lung, but also promotes robust immunity comprising significantly elevated systemic, cellular, and mucosal immune responses, which is in stark contrast to intramuscular injected counterpart that displays less pronounced benefits. Our findings offer new insight into the development of mucosal mRNA therapeutics from an overlooked but crucial perspective of optimizing mRNA components.

synthetic biology↗

bioRxiv2024

Shade Inhibits Cambial Activity in Populus Stems by the SPL16/SPL23-Mediated Cytokinin Pathway

Trees in natural forests or plantations often encounter neighbor proximity signal that negatively impacts wood production. However, the molecular basis underlying shade-regulation of vascular cambial activity during stem radial growth remains unknown in woody species. Here, we revealed that high stand density and simulated shade (low R/FR ratio) suppress the division and differentiation of cambial cells in poplar stems. A genome-wide screen for Populus SQUAMOSA PROMOTER BINDING PROTEIN-LIKE (SPL) genes identified that SPL16 and SPL23 are preferentially expressed in the phloem and cambium, being downregulated by simulated shade. Knocking out SPL16/23 impaired cambial activity, whereas phloem-specific overexpression of SPL16 stimulated cambial proliferation and mitigated the shade-inhibition of cambial activity. Additionally, shade decreased bioactive cytokinin (CK) levels by suppressing the expression of CK biosynthesis genes IPT5a, IPT5b and LOG1b in poplar stems. Molecular and genetic studies reveled that SPL16/23 directly activate IPT5s/LOG1b expression to promote CK biosynthesis and cambial activity. Moreover, elevated miR156 expression in shade-treated stems regulated SPL16/23 at the post-transcriptional level, mediating shades effects on cambial activity. Collectively, our findings unravel that the miR156-SPL16/23-IPT5/LOG1-cytokinin pathway operates in the shade-mediated inhibition of cambial activity, providing potential targets for the genetic improvement of shade-tolerant trees.

plant biology↗

bioRxiv2024

Comparative study on the effects of different types of acute exercise on cortisol levels and cognitive functions

This study examines the different effects of dual-task and single-task exercises on cortisol levels and cognitive performance. Seventeen male college students participated, performing each exercise on separate days. Salivary samples were taken before and after exercise to assess cortisol levels. Cognitive functions were measured using the 2-Back Test, Bells Test, and Mental Rotation Test. Results showed that both exercises significantly improved reaction times across cognitive tests. However, dual-task exercise caused a more notable increase in cortisol levels (p=0.002) than the single-task. A negative correlation between post-exercise cortisol levels and reaction times suggests that higher cortisol levels might enhance cognitive processing speed. Cognitive performance ac-curacy remained unchanged across both exercises. These findings indicate that while both exercise types enhance cognitive speed, dual-task exercise triggers a greater cortisol response, potentially offering more benefits for cognitive processing speed without affecting accuracy. This research highlights the complex interaction between acute exercise, stress hormones, and cognitive function, providing insights into how different exercise types influence cognitive performance through hormonal pathways.

neuroscience↗

bioRxiv2024

Spatial and Single Cell Mapping of Castleman Disease Reveals Key Stromal Cell Types and Cytokine Pathways

Castleman disease (CD) is inflammatory lymphoproliferative disorder of unclear etiology. To determine the cellular and molecular basis of CD, we analyzed the spatial proteome of 4,485,009 single cells, transcriptome of 50,117 single nuclei, immune repertoire of 8187 single nuclei, and pathogenic mutations in Unicentric CD, idiopathic Multicentric CD, HHV8-associated MCD, and reactive lymph nodes. CD was characterized by increased non-lymphoid and stromal cells that formed unique microenvironments where they interacted with lymphoid cells. Interaction of activated follicular dendritic cell (FDC) cytoplasmic meshworks with mantle zone B cells was associated with B cell activation and differentiation. VEGF, IL-6, MAPK, and extracellular matrix pathways were elevated in stromal cells of CD. CXCL13+ FDCs, PDGFRA+ T-zone reticular cells (TRC), and ACTA2-positive perivascular reticular cells (PRC) were identified as the predominant source of increased VEGF expression and IL-6 signaling in CD. VEGF expression by FDCs was associated with peri-follicular neovascularization. FDC, TRC and PRC of CD activated JAK-STAT, TGF{beta}, and MAPK pathways via ligand-receptor interactions involving collagen, integrins, complement components, and VEGF receptors. T, B and plasma cells were polyclonal but showed class-switched and somatically hypermutated IgG1+ plasma cells consistent with stromal cell-driven germinal center activation. In conclusion, our findings show that stromal cell activation and associated B-cell activation and differentiation, neovascularization and stromal remodeling underlie CD and suggest new targets for treatment. Key pointsO_LICastleman Disease is characterized by activation and proliferation of CXCL13+ FDCs, PDGFRA+ reticular cells, and ACTA2-positive PRCs. C_LIO_LIVEGF and IL-6 from lymph node stromal cells are associated with B-cell activation and differentiation, endothelial proliferation, and inflammation in CD C_LI

pathology↗

bioRxiv2024

Protein Arginine Methylation of the Translation Initiation Factor eIF1A Increases Usage of a Near-cognate Start Codon

Protein arginine methylation has emerged as a key post-translational modification responsible for many facets of eukaryotic gene expression. To better understand the extent of this modification in cellular pathways, we carried out bioorthogonal methylation profiling in Saccharomyces cerevisiae to comprehensively identify the in vivo substrates of the major yeast protein arginine methyltransferase Hmt1. Gene ontology analysis of candidate substrates revealed an enrichment of proteins involved in the process of translation. We verified one such factor, eIF1A, by in vitro methylation. Three sites on eIF1A were found to be responsible for its methylation: R13, R14, and R62, with varied capacity by which each site contributed to the overall methylation capacity in vitro. To determine the role of methylation in eIF1A function, we used a battery of arginine-to-alanine substitution mutants to evaluate translation fidelity in these mutants. Our data show that substitution mutants at R13 and R14 in the N-terminal tail improved the fidelity of start codon recognition in an initiation fidelity assay. Overall, our data suggest that Hmt1-mediated methylation of eIF1A fine-tunes the fidelity of start codon recognition for proper translation initiation.

molecular biology↗