Biology subjects

Wiley, M.

Publications and source records attributed to Wiley, M..

3 recordsLinked to original sources

bioRxiv2018

Evidence of an Unusual Poly(A) RNA Signature Detected by High-throughput Chemical Mapping

Homopolymeric adenosine RNA plays numerous roles in both cells and non-cellular genetic material, and for lack of evidence to the contrary, it is generally accepted to form a random coil under physiological conditions. However, chemical mapping data generated by the Eterna Massive Open Laboratory indicates that a poly (A) sequence of length seven or more, at pH 8.0 and MgCl concentrations of 10 mM, develops unexpected protection to selective 2-hydroxyl acylation read out by primer extension (SHAPE) and dimethyl sulfate (DMS) chemical probing. This protection first appears in poly(A) sequences of length 7 and grows to its maximum strength at length ~10. In a long poly(A) sequence, substitution of a single A by any other nucleotide disrupts the protection, but only for the 6 or so nucleotides on the 5 side of the substitution. The authors are grateful for pre-publication comments; please use https://docs.google.com/document/d/14972Q36IDTYMglwMXTOrqd4P9orQ6-P3bPbCuITdv6A.

biochemistry↗

bioRxiv2018

bpRNA: Large-scale Automated Annotation and Analysis of RNA Secondary Structure

While RNA secondary structure prediction from sequence data has made remarkable progress, there is a need for improved strategies for annotating the features of RNA secondary structures. Here we present bpRNA, a novel annotation tool capable of parsing RNA structures, including complex pseudoknot-containing RNAs, to yield an objective, precise, compact, unambiguous, easily-interpretable description of all loops, stems, and pseudoknots, along with the positions, sequence, and flanking base pairs of each such structural feature. We also introduce several new informative representations of RNA structure types to improve structure visualization and interpretation. We have further used bpRNA to generate a web-accessible meta-database, \"bpRNA-1m\", of over 100,000 single-molecule, known secondary structures; this is both more fully and accurately annotated and over 20-times larger than existing databases. We use a subset of the database with highly similar ([≥]90% identical) sequences filtered out to report on statistical trends in sequence, flanking base pairs, and length. Both the bpRNA method and the bpRNA-1m database will be valuable resources both for specific analysis of individual RNA molecules and large-scale analyses such as are useful for updating RNA energy parameters for computational thermodynamic predictions, improving machine learning models for structure prediction, and for benchmarking structure-prediction algorithms.

bioinformatics↗

bioRxiv2017

Interferon Regulatory Factor 5 (IRF5) Interacts with the Translation Initiation Complex and Promotes mRNA Translation During the Integrated Stress Response to Amino Acid Deprivation

Interferon Regulatory Factor 5 (IRF5) plays an important role in limiting pathogenic infection and tumor development. Host protection by IRF5 can occur through a variety of mechanisms including production of type I interferon and cytokines as well as the regulation of cell survival, growth, proliferation, and differentiation. While modulation of these cellular processes is attributed to IRF5 transcription factor function in the nucleus, emerging evidence suggests that IRF5 may also retain non-transcriptional regulatory properties within the cytoplasmic compartment. Consistent with this notion, we report the ability of IRF5 to control gene expression at the level of mRNA translation. Our findings demonstrate that IRF5 interacts with the translation initiation complex in the absence of the m7GTP cap-binding protein, eIF4E. We observed that under nutrient deprivation-induced cell stress, IRF5 promoted mRNA translation of the master integrated stress response (ISR) regulator, Activating Transcription Factor 4 (ATF4). Enhanced ATF4 protein expression correlated with increased levels of downstream target genes including CHOP and GADD34 and was associated with amplification of eIF2 de-phosphorylation and translational de-repression under stress. The novel mechanism we describe broadens our understanding of how IRF5 regulates gene expression and may govern diverse cellular processes in the absence of stimuli that trigger IRF5 nuclear translocation.

biochemistry↗