Antisense RNAs during early vertebrate development are divided in groups with distinct features

Sanjana Pillay; Hazuki Takahashi; Piero Carninci; Aditi Kanhere

doi:10.1101/gr.262964.120

Antisense RNAs during early vertebrate development are divided in groups with distinct features

¹ Mount Sinai School of Medicine;
² RIKEN Yokohama Campus;
³ University of Liverpool

↵* Corresponding author; email: a.kanhere{at}liverpool.ac.uk

Abstract

Long noncoding RNAs or lncRNAs are a class of non-protein-coding RNAs that are >200 nucleotides in length. Almost 50% of lncRNAs during zebrafish development are transcribed in an antisense direction to a protein-coding gene. However, the role of these Natural Antisense Transcripts or NATs during development remains enigmatic. To understand NATs in early vertebrate development, we took a computational biology approach and analyzed existing as well as novel datasets. Our analysis indicates that zebrafish NATs can be divided into two major classes based on their coexpression patterns with respect to the overlapping protein-coding genes. Group-1 NATs have characteristics similar to maternally deposited RNAs in that their levels decrease as development progresses. Group-1 NAT levels are negatively correlated with that of overlapping sense-strand protein-coding genes. Group-2 NATs, on the other hand, are coexpressed with overlapping protein-coding genes. In contrast to group-1, which is enriched in genes involved in developmental pathways, group-2 protein-coding genes are enriched in housekeeping functions. Group-1 NATs also show larger overlap and higher complementarity with the sense-strand mRNAs as compared to other NATs. In addition, our transcriptomics data, quantifying RNA levels from cytoplasmic and nuclear compartments, indicates that group-1 NATs are more populated in the cytosol. Based on their expression pattern, cytosolic nature and their higher complementarity to the overlapping developmental mRNAs, we speculate that group-1 NATs function post-transcriptionally to silence spurious expression of developmental genes.

Received March 2, 2020.
Accepted March 29, 2021.

Published by Cold Spring Harbor Laboratory Press

This manuscript is Open Access.

This article, published in Genome Research, is available under a Creative Commons License (Attribution 4.0 International license), as described at http://creativecommons.org/licenses/by/4.0/.