Abstract

Long intergenic non-coding RNAs (lincRNAs) associated with a number of cancers and other diseases have been identified in mammals, but they are still formidable to be comprehensively identified and characterized. Marek’s disease (MD) is a T cell lymphoma of chickens induced by Marek’s disease virus (MDV). Here, we used a MD chicken model to develop a precise pipeline for identifying lincRNAs and to determine the roles of lincRNAs in T cell tumorigenesis. More than 1,000 lincRNA loci were identified in chicken bursa. Computational analyses demonstrated that lincRNAs are conserved among different species such as human, mouse and chicken. The putative lincRNAs were found to be associated with a wide range of biological functions including immune responses. Interestingly, we observed distinct lincRNA expression signatures in bursa between MD resistant and susceptible lines of chickens. One of the candidate lincRNAs, termed linc-satb1, was found to play a crucial role in MD immune response by regulating a nearby protein-coding gene SATB1. Thus, our results manifested that lincRNAs may exert considerable influence on MDV-induced T cell tumorigenesis and provide a rich resource for hypothesis-driven functional studies to reveal genetic mechanisms underlying susceptibility to tumorigenesis.

Highlights

  • Expression, localization to subcellular compartments, response to stimulus, shared synteny across species, and association with disease, suggesting that they are regulated and unlikely represent transcriptional “noise”[16,17,18,19,20]

  • Transcriptomic sequencing was used to interrogate the whole transcriptome of chicken bursa over three time-points corresponding to critical phases of Marek’s disease virus (MDV) infection

  • By using ab-initio transcriptome assembly followed by stringent lincRNA identification criteria, more than 1,000 candidate lincRNA loci were ascertained in Marek’s disease (MD) chickens

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Summary

Introduction

Expression, localization to subcellular compartments, response to stimulus, shared synteny across species, and association with disease, suggesting that they are regulated and unlikely represent transcriptional “noise”[16,17,18,19,20]. The most direct evidence for a transcript to be classified as non-coding is that no protein product is produced from the putative open reading frame (ORF); one of the most frequently used criteria is the length of ORF29. Another strategy is to search three-frame translated peptide sequences against known protein or protein domain database To precisely identify lincRNAs, a series of constrains were applied to filter non-lincRNAs. a relatively reliable and solid pipeline was developed for lincRNAs identification and potential biological function exploration. We believe that this study will provide valuable lincRNAs information in chicken and advance our knowledge of non-coding RNA biology, especially on MD

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