Sense-oriented AluYRa1 elements provide a lineage-specific transcription environment for polyadenylation

Hyeon-Mu Cho,Hee-Eun Lee,Hye-Ri Park,Sang-Je Park,Ja-Rang Lee,Se-Hee Choe,Jae-Won Huh,Young-Hyun Kim

doi:10.1038/s41598-021-83360-4

Abstract

Transposable elements cause alternative splicing (AS) in different ways, contributing to transcript diversification. Alternative polyadenylation (APA), one of the AS events, is related to the generation of mRNA isoforms in 70% of human genes. In this study, we tried to investigate AluYRa1s located at the terminal region of cynomolgus monkey genes, utilizing both computational analysis and molecular experimentation. We found that ten genes had AluYRa1 at their 3′ end, and nine of these AluYRa1s were sense-oriented. Furthermore, in seven genes, AluYRa1s were expected to have a similar consensus sequence for polyadenylation cleavage. Additional computational analysis using the annotation files from the UCSC database showed that AluYRa1 was more involved in polyadenylation than in open reading frame exon splicing. To examine the extent of AluYRa1 involvement in polyadenylation, RNA-seq data from 30 normal cynomolgus monkeys were analyzed using TAPAS, a recently devised software that detects all the promising polyadenylation sites including APA sites. We observed that approximately 74% of possible polyadenylation sites in the analyzed genes were provided by sense-oriented AluYRa1. In conclusion, AluYRa1 is an Old-World monkey-specific TE, and its sense-oriented insertion at the 3′UTR region tends to provide a favorable environment for polyadenylation, diversifying gene transcripts.

Highlights

Transposable elements cause alternative splicing (AS) in different ways, contributing to transcript diversification
We counted the number of genes that have a 3′UTR end located at AluYRa1 via computational calculations
We found that the transcripts of seven genes (TK2, PEX26, GTPBP4, IRF9, BLOC1S6, UBE2B, PAICS) had 3′UTR end AluYRa1 sequences

Summary

Introduction

Transposable elements cause alternative splicing (AS) in different ways, contributing to transcript diversification. Alternative polyadenylation (APA), one of the AS events, is related to the generation of mRNA isoforms in 70% of human genes. We observed that approximately 74% of possible polyadenylation sites in the analyzed genes were provided by sense-oriented AluYRa1. AluYRa1 is an Old-World monkey-specific TE, and its sense-oriented insertion at the 3′UTR region tends to provide a favorable environment for polyadenylation, diversifying gene transcripts. Transposable elements (TEs) are repetitive movable DNA sequences on the g enome[1] They serve as driving forces contributing to genome evolution and are pathogenic elements for numerous diseases[2]. All natural genomes are significantly influenced by these mobile elements in many different ways[5], leading to alternative splicing (AS), a post-transcriptional process that causes alterations in the exon s tructure[6]. The location where polyadenylation occurs, at 3′UTR or upstream of the 3′ of most exons, is proven to be crucial because it correlates with protein expression and localization[14]

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Conclusion