Spliceosomal snRNA Epitranscriptomics.

Pedro Morais,Hironori Adachi,Yi-Tao Yu

doi:10.3389/fgene.2021.652129

Abstract

Small nuclear RNAs (snRNAs) are critical components of the spliceosome that catalyze the splicing of pre-mRNA. snRNAs are each complexed with many proteins to form RNA-protein complexes, termed as small nuclear ribonucleoproteins (snRNPs), in the cell nucleus. snRNPs participate in pre-mRNA splicing by recognizing the critical sequence elements present in the introns, thereby forming active spliceosomes. The recognition is achieved primarily by base-pairing interactions (or nucleotide-nucleotide contact) between snRNAs and pre-mRNA. Notably, snRNAs are extensively modified with different RNA modifications, which confer unique properties to the RNAs. Here, we review the current knowledge of the mechanisms and functions of snRNA modifications and their biological relevance in the splicing process.

Highlights

Pre-mRNA splicing is, by definition, a co- or post-transcriptional RNA processing reaction by which introns are removed from mRNA precursors, and exons are precisely joined together to form functional mature mRNAs (Berget et al, 1977; Chow et al, 1977; Shi, 2017)
As to the possible mechanism, the authors of this study hypothesized that the modified adenosine (m6Am30) could potentially be involved in the recruitment of U2 snRNA to the branch site by U2 auxiliary factor (U2AF) (Zamore et al, 1992; Zhang et al, 1992), a heterodimer that recognizes and binds to the 3' splice site at an early stage of spliceosome assembly, affecting the pre-mRNA splicing process (Figure 2)
Understanding the splicing mechanisms at the molecular level is of critical importance to fully comprehend gene expression and to develop new nucleic acid-based therapeutics, such as splice-switching oligonucleotides (Lim and Yokota, 2018), aimed at correcting splicing-associated mutations that lead to aberrant proteins and diseases. pre-mRNA splicing occurs in the spliceosome, an extremely large complex consisting of five snRNAs and a large number of proteins that interact with substrate pre-mRNA in a highly orchestrated manner

Summary

Introduction

Pre-mRNA splicing is, by definition, a co- or post-transcriptional RNA processing reaction by which introns are removed from mRNA precursors, and exons are precisely joined together to form functional mature mRNAs (Berget et al, 1977; Chow et al, 1977; Shi, 2017). 2'-O-methylation at position 70 (Krogh et al, 2017) is likely catalyzed by an RNA-dependent mechanism, given that a box C/D RNA (SCARNA7, known as U90) has been identified to target this site (Darzacq et al, 2002).

Results

Conclusion