Genome-wide perturbations of Alu expression and Alu-associated post-transcriptional regulations distinguish oligodendroglioma from other gliomas

Taeyoung Hwang,Ho Kang,Jae-Kyung Won,Sung-Hye Park,Sojin Kim,Chul-Kee Park,Joo Heon Shin,Tamrin Chowdhury,Kyung-Min Kim,Hyeon Jong Yu

doi:10.1038/s42003-022-03011-w

Abstract

Alu is a primate-specific repeat element in the human genome and has been increasingly appreciated as a regulatory element in many biological processes. But the appreciation of Alu has been limited in tumorigenesis, especially for brain tumor. To investigate the relevance of Alu to the gliomagenesis, we studied Alu element-associated post-transcriptional processes and the RNA expression of the element by performing RNA-seq for a total of 41 pairs of neurotypical and diverse glioma brain tissues. We find that A-to-I editing and circular RNA levels, as well as Alu RNA expression, are decreased overall in gliomas, compared to normal tissue. Interestingly, grade 2 oligodendrogliomas are least affected in A-to-I editing and circular RNA levels among gliomas, whereas they have a higher proportion of down-regulated Alu subfamilies, compared to the other gliomas. These findings collectively imply a unique pattern of Alu-associated transcriptomes in grade 2 oligodendroglioma, providing an insight to gliomagenesis from the perspective of an evolutionary genetic element.

Highlights

Alu is a primate-specific repeat element in the human genome and has been increasingly appreciated as a regulatory element in many biological processes
We performed strand-specific RNAseq for tumor and matched normal samples obtained from 41 patients across various pathologies of gliomas spanning isocitrate dehydrogenase (IDH) mutant and 1p/19q-codeleted oligodendroglioma grades 2 and 3 (O2 and O3), IDH mutant astrocytoma grades 2, 3 and 4 (A2, A3, and A4), and GBM (Supplementary Table 1)
We identified that some numbers (3415) of A-to-I editing sites were found in all the patients and they had a potential to cluster samples into tumor and normal tissues (Supplementary Fig. 2 and Supplementary Data 1), which implies that these A-to-I editing sites are regulated in human brain tissues, despite the variability of individual samples

Summary

Introduction

Alu is a primate-specific repeat element in the human genome and has been increasingly appreciated as a regulatory element in many biological processes. We find that A-to-I editing and circular RNA levels, as well as Alu RNA expression, are decreased overall in gliomas, compared to normal tissue. Grade 2 oligodendrogliomas are least affected in A-to-I editing and circular RNA levels among gliomas, whereas they have a higher proportion of down-regulated Alu subfamilies, compared to the other gliomas. These findings collectively imply a unique pattern of Alu-associated transcriptomes in grade 2 oligodendroglioma, providing an insight to gliomagenesis from the perspective of an evolutionary genetic element. Alu RNA has been reported to influence translation[17]

Methods

Results

Conclusion