Regulation of the Alternative Neural Transcriptome by ELAV/Hu RNA Binding Proteins.

Lu Wei,Eric C Lai

doi:10.3389/fgene.2022.848626

Abstract

The process of alternative polyadenylation (APA) generates multiple 3' UTR isoforms for a given locus, which can alter regulatory capacity and on occasion change coding potential. APA was initially characterized for a few genes, but in the past decade, has been found to be the rule for metazoan genes. While numerous differences in APA profiles have been catalogued across genetic conditions, perturbations, and diseases, our knowledge of APA mechanisms and biology is far from complete. In this review, we highlight recent findings regarding the role of the conserved ELAV/Hu family of RNA binding proteins (RBPs) in generating the broad landscape of lengthened 3' UTRs that is characteristic of neurons. We relate this to their established roles in alternative splicing, and summarize ongoing directions that will further elucidate the molecular strategies for neural APA, the in vivo functions of ELAV/Hu RBPs, and the phenotypic consequences of these regulatory paradigms in neurons.

Highlights

The 3’ untranslated region (3’ UTR) is a hub of post-transcriptional regulation by RNA binding proteins and miRNAs, which collectively mediate diverse functional impacts including alteration of mRNA stability, directing transcript subcellular localization, modulating translational efficiency and/ or changing protein function (Tian and Manley, 2017; Gruber and Zavolan, 2019)
Subcellular transcriptome mapping of the binding sites of individual ELAV/Hu RNA binding proteins (RBPs) may help to identify fundamental cis-elements associated with specific groups of poly(A) signals (PAS) which are bypassed under the regulation of Hu family proteins, and whether there are distinctions between internal alternative splicing targets for exclusion or inclusion
The fact that ectopic expression of Drosophila ELAV/Hu RBPs can confer neuronal-like splicing and alternative polyadenylation (APA) profiles to non-neural cell types (Oktaba et al, 2015; Wei et al, 2020; Lee et al, 2021) indicates that gain-of-function approaches are a viable alternative to interrogate the activities of an overlapping family

Summary

Introduction

The 3’ untranslated region (3’ UTR) is a hub of post-transcriptional regulation by RNA binding proteins and miRNAs, which collectively mediate diverse functional impacts including alteration of mRNA stability, directing transcript subcellular localization, modulating translational efficiency and/ or changing protein function (Tian and Manley, 2017; Gruber and Zavolan, 2019). Members of the conserved ELAV/Hu RNA binding protein (RBP) family have received growing attention as global mediators of both neural-specific splicing and APA programs (Carrasco et al, 2020; Wei et al, 2020; Lee et al, 2021).

Results

Conclusion