LINC01013 is a determinant of fibroblast activation and encodes a novel fibroblast-activating micropeptide
LINC01013 is a determinant of fibroblast activation and encodes a novel fibroblast-activating micropeptide
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.
77-85
Quaife, N.M.
086acd79-3c9b-4271-a187-f4479f6e6ce0
Chothani, S.
aa1b1b29-6f22-4931-9fa6-6f4ad0b1cc2e
Schulz, J.F.
bd699684-b6ac-4383-b0f5-4e6f323d17fb
Rackham, O.
8122eb1f-6e9f-4da5-90e1-ce108ccbbcbf
27 June 2022
Quaife, N.M.
086acd79-3c9b-4271-a187-f4479f6e6ce0
Chothani, S.
aa1b1b29-6f22-4931-9fa6-6f4ad0b1cc2e
Schulz, J.F.
bd699684-b6ac-4383-b0f5-4e6f323d17fb
Rackham, O.
8122eb1f-6e9f-4da5-90e1-ce108ccbbcbf
Quaife, N.M., Chothani, S. and Schulz, J.F.
,
et al.
(2022)
LINC01013 is a determinant of fibroblast activation and encodes a novel fibroblast-activating micropeptide.
Journal of Cardiovascular Translational Research, 16, .
(doi:10.1007/s12265-022-10288-z).
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.
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s12265-022-10288-z
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Accepted/In Press date: 9 June 2022
Published date: 27 June 2022
Additional Information:
A correction to this research output can be found at: https://doi.org/10.1007/s12265-022-10291-4
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Local EPrints ID: 502729
URI: http://eprints.soton.ac.uk/id/eprint/502729
ISSN: 1937-5387
PURE UUID: 7759122e-5bb7-4cdd-aa34-eaff882f12a1
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Date deposited: 07 Jul 2025 16:46
Last modified: 22 Aug 2025 02:30
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Author:
N.M. Quaife
Author:
S. Chothani
Author:
J.F. Schulz
Corporate Author: et al.
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