Biology subjects

Erady, C.

Publications and source records attributed to Erady, C..

3 recordsLinked to original sources

bioRxiv2020

Use of short-read RNA-Seq data to identify transcripts that can translate novel ORFs

Identification of as of yet unannotated or undefined novel open reading frames (nORFs) and exploration of their functions in multiple organisms has revealed that vast regions of the genome have remained unexplored or hidden. Present within both protein-coding and noncoding regions, these nORFs signify the presence of a much more diverse proteome than previously expected. Given the need to study nORFs further, proper identification strategies must be in place, especially because they cannot be identified using conventional gene signatures. Although Ribo-Seq and proteogenomics are frequently used to identify and investigate nORFs, in this study, we propose a workflow for identifying nORF containing transcripts using our precompiled database of nORFs with translational evidence, using sample transcript information. Further, we discuss the potential uses of this identification, the caveats involved in such a transcript identification and finally present a few representative results from our analysis of naive mouse B and T cells, human post-mortem brain and cichlid fish transcriptome. Our proposed workflow can identify noncoding transcripts that can potentially translate intronic, intergenic and several other classes of nORFs. One-line summaryA systematic workflow to identify nORF containing transcripts using sample transcript information.

genomics↗

bioRxiv2019

Translational products encoded by novel ORFs may form protein-like structures and have biological functions

Translation products encoded by non canonical or novel open reading frame (ORF) genomic regions are generally considered too small to play any significant biological role, and dismissed as inconsequential. In this study, we show that mutations mapping to novel ORFs have significantly higher pathogenicity scores than mutations in protein-coding regions. Importantly, novel ORFs can translate into protein-like structures with putative independent biological functions that can be of relevance in disease states, including cancer. We thus provide strong evidence to support the systematic study of novel ORFs to gain new insights into normal biological and disease processes.\n\nOne Sentence SummaryNon coding regions may encode protein-like products that are important to understand diseases.

genetics↗

bioRxiv2018

Cell-matrix adhesion controls Golgi organization and function by regulating Arf1 activation in anchorage-dependent cells.

Cell-matrix adhesion regulates membrane trafficking to control anchorage-dependent signaling. While a dynamic Golgi complex can contribute to this pathway, its control by adhesion remains untested. We find the loss of adhesion rapidly disorganizes the Golgi in mouse and human fibroblast cells, its integrity restored rapidly on re-adhesion to fibronectin (but not poly-l-lysine coated beads) along the microtubule network. Adhesion regulates the trans-Golgi more prominently than the cis /cis-medial Golgi, though they show no fallback into the ER making this reorganization distinct from known Golgi fragmentation. This is controlled by an adhesion-dependent drop and recovery of Arf1 activation, mediated through the Arf1 GEF BIG1/2 over GBF1. Constitutively active Arf1 disrupts this regulation and prevents Golgi disorganization in non-adherent cells. Adhesion regulates active Arf1 binding to the microtubule minus-end motor protein dynein to control Golgi reorganization, which ciliobrevin blocks. This regulation by adhesion controls Golgi function, promoting cell surface glycosylation on the loss of adhesion that constitutively active Arf1 blocks. This study hence identifies cell-matrix adhesion to be a novel regulator of Arf1 activation, controlling Golgi organization and function in anchorage-dependent cells.\n\nSummary StatementThis study identifies a role for cell-matrix adhesion in regulating organelle (Golgi) architecture and function which could have implications for multiple cellular pathways and function.

cell biology↗