Abstract

BackgroundA great mass of long noncoding RNAs (lncRNAs) have been identified in mouse genome and increasing evidences in the last decades have revealed their crucial roles in diverse biological processes. Nevertheless, the biological roles of lncRNAs in the mouse retina remains largely unknown due to the lack of a comprehensive annotation of lncRNAs expressed in the retina.ResultsIn this study, we applied the long-reads sequencing strategy to unravel the transcriptomes of developing mouse retinas and identified a total of 940 intergenic lncRNAs (lincRNAs) in embryonic and neonatal retinas, including about 13% of them were transcribed from unannotated gene loci. Subsequent analysis revealed that function of lincRNAs expressed in mouse retinas were closely related to the physiological roles of this tissue, including 90 lincRNAs that were differentially expressed after the functional loss of key regulators of retinal ganglion cell (RGC) differentiation. In situ hybridization results demonstrated the enrichment of three class IV POU-homeobox genes adjacent lincRNAs (linc-3a, linc-3b and linc-3c) in ganglion cell layer and indicated they were potentially RGC-specific.ConclusionsIn summary, this study systematically annotated the lincRNAs expressed in embryonic and neonatal mouse retinas and implied their crucial regulatory roles in retinal development such as RGC differentiation.

Highlights

  • A great mass of long noncoding RNAs have been identified in mouse genome and increasing evidences in the last decades have revealed their crucial roles in diverse biological processes

  • Iso-seq and error correction Sequencing of pooled mouse retinal RNAs generated a total of 5,084,169 subreads from six SMAT cells of combined SMRTbell libraries, which formed 372,267 higher quality circular consensus sequences (CCSs). 295,179 full-length non chimera (FLNC) sequences, i.e., CCSs containing the 5′- and 3′primers and polyA tails, were subsequently clustered and polished by using non full-length (NFL) sequences that yielded a total of 172,333 consensus sequences

  • Long-reads sequencing and subsequent analysis in this study identified hundreds of retinal intergenic long noncoding RNA (lincRNA), which showed the high complexity of long noncoding RNA (lncRNA) genes in transcription and the high specificity in retina tissue

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Summary

Introduction

A great mass of long noncoding RNAs (lncRNAs) have been identified in mouse genome and increasing evidences in the last decades have revealed their crucial roles in diverse biological processes. Vertebrate retinas shares a highly organized and conserved structure, and is an excellent system to study the differentiation and development of neurons [1, 2]. Increasing pieces of evidence in the last decade point to the crucial regulatory roles of LncRNAs are defined as a class of RNAs greater than 200 nucleotides in length and without detectable coding potential [10]. It is widely accepted that lncRNAs play pivotal regulatory roles in diverse biological processes, such as imprinting, cell cycle regulation, cell differentiation, and other developmental processes [12, 13]. For instance, Tug is necessary for photoreceptor formation [14], Miat ( known as Rncr or Gomafu) and Six3OS are involved in regulating the retinal cell fate specification [15, 16], Vax2os is involved in the control of

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