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LINC01013 is a determinant of fibroblast activation and encodes a novel fibroblast-activating micropeptide

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Item Type:Article
Title:LINC01013 is a determinant of fibroblast activation and encodes a novel fibroblast-activating micropeptide
Creators Name:Quaife, N.M. and Chothani, S. and Schulz, J.F. and Lindberg, E.L. and Vanezis, K. and Adami, E. and O'Fee, K. and Greiner, J. and Litviňuková, M. and van Heesch, S. and Whiffin, N. and Hubner, N. and Schafer, S. and Rackham, O. and Cook, S.A. and Barton, P.J.R.
Abstract:Myocardial fibrosis confers an almost threefold mortality risk in heart disease. There are no prognostic therapies and novel therapeutic targets are needed. Many thousands of unannotated small open reading frames (smORFs) have been identified across the genome with potential to produce micropeptides (< 100 amino acids). We sought to investigate the role of smORFs in myocardial fibroblast activation.Analysis of human cardiac atrial fibroblasts (HCFs) stimulated with profibrotic TGFβ1 using RNA sequencing (RNA-Seq) and ribosome profiling (Ribo-Seq) identified long intergenic non-coding RNA LINC01013 as TGFβ1 responsive and containing an actively translated smORF. Knockdown of LINC01013 using siRNA reduced expression of profibrotic markers at baseline and blunted their response to TGFβ1. In contrast, overexpression of a codon-optimised smORF invoked a profibrotic response comparable to that seen with TGFβ1 treatment, whilst FLAG-tagged peptide associated with the mitochondria.Together, these data support a novel LINC01013 smORF micropeptide-mediated mechanism of fibroblast activation.
Keywords:Myocardial Fibrosis, lncRNA, Micropeptide, Small Open Reading Frame, Translation
Source:Journal of cardiovascular translational research
ISSN:1937-5395
Publisher:Springer
Date:27 June 2022
Additional Information:Erratum in: J Cardiovasc Transl Res 14 July 2022
Official Publication:https://doi.org/10.1007/s12265-022-10288-z
PubMed:View item in PubMed

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