Akimoto

Anderson

Asakura

Bartel

Berleth

Blentic

Carthew

Cauthen

Chen

Darnell

Friedman

Goljanek–Whysall

Greco

Griffiths–Jones

Grimson

Hinits

Hirai

Huang

Inose

Katagiri

Klochendler–Yeivin

Krek

Krützfeldt

Lewis

Lickert

Lopez–Rodríguez

Mankoo

Mollard

Nakajima

O'Connor

Rajewsky

Ramjaun

Rathjen

Reijntjes

Ricotti

Salucci

Shan

Sweetman

Swingler

Tuddenham

van Rooij

Wang

Wienholds

Yamamoto–Mizuma

English

Summary
               MicroRNAs are short non-coding RNAs involved in post-transcriptional regulation of multiple messenger RNA targets. The miR-1/miR-206 family is expressed during skeletal muscle differentiation and is an integral component of myogenesis. To better understand miR-1/miR-206 function during myoblast differentiation we identified novel target mRNAs by microarray and characterized their function in C2C12 myoblasts. Candidate targets from the screen were experimentally validated together with target genes that were predicted by three different algorithms. Some targets characterised have a known function in skeletal muscle development and/or differentiation and include Meox2, RARB, Fzd7, MAP4K3, CLCN3 and NFAT5, others are potentially novel regulators of myogenesis, such as the chromatin remodelling factors Smarcd2 and Smarcb1 or the anti-apoptotic protein SH3BGRL3. The expression profiles of confirmed target genes were examined during C2C12 cell myogenesis. We found that inhibition of endogenous miR-1 and miR-206 by antimiRs blocked the downregulation of most targets in differentiating cells, thus indicating that microRNA activity and target interaction is required for muscle differentiation. Finally, we show that sustained expression of validated miR-1 and/or miR-206 targets resulted in increased proliferation and inhibition of C2C12 cell myogenesis. In many cases the expression of genes related to non-muscle cell fates, such as chondrogenesis, was activated. This indicates that the concerted downregulation of multiple microRNA targets is not only crucial to the skeletal muscle differentiation program but also serves to prevent alternative cell fate choices.</jats:p

Katarzyna Goljanek-Whysall

Helio Pais

Tina Rathjen

Dylan Sweetman

Tamas Dalmay

Andrea Münsterberg

Crossref

Journal of Cell Science

Regulation of multiple target genes by miR-1 and miR-206 is pivotal for C2C12 myoblast differentiation

Regulation of multiple target genes by miR-1 and miR-206 is pivotal for C2C12 myoblast differentiation

Abstract

Similar works

Full text

Available Versions

Crossref

University of East Anglia digital repository

Crossref