Long Noncoding RNA Lnc-SEMT Modulates IGF2 Expression by Sponging miR-125b to Promote Sheep Muscle Development and Growth

Cell Physiol Biochem. 2018;49(2):447-462. doi: 10.1159/000492979. Epub 2018 Aug 28.

Abstract

Background/aims: Long noncoding RNAs (lncRNAs) are RNA transcripts that are more than 200 nt long but have little protein-coding potential. Within the last few years, thousands of lncRNAs have been identified and their functions in biological processes have begun to be understood. Although many studies havebegun to examine the functions of many noncoding RNAs, very little is known about the functions of long noncoding (lncRNA) function of livestock production and molecular mechanisms of their functions are still lackingrelated to livestock production.

Methods: Expression of sheep enhanced muscularityTranscript lncRNA (lnc-SEMT) and miR-125b were examined in sheep using quantitative reverse-transcription polymerase chain reaction. Expression of Myod (myogenic determination factor), Myog (myoglobin) and Insulin-like growth factor 2 (IGF2)were examined by Western Blot.Luciferase reporter assays were performedto confirm the relationship between lnc-SEMT and miR-125b.

Results: Here, we identified a novel lnc-SEMT that promote sheep myoblast differentiation in vitro and enhanced sheep muscularity in vivo. Functional analyses showed that lnc-SEMT accelerates sheep myoblast differentiation in vitro. lnc-SEMT transgenic sheep exhibit a muscle hypertrophy phenotype characterized by increased body weight, and increased the number of muscle fibers indicating that lnc-SEMT play an important role in the regulation of skeletal muscle differentiation in vivo. Our results show that lnc-SEMT acts as a molecular sponge by antagonizing miR-125b to control IGF2 protein labundance in vitro and in vivo.

Conclusion: In brief, lnc-SEMT is the first example of a lncRNA could be a useful candidate for improving biological growth traits such as skeletal muscle production in sheep.

Keywords: IGF2; LncRNA; miR-125b; myoblast differentiation; sheep muscularity.

MeSH terms

  • 3' Untranslated Regions
  • Animals
  • Animals, Genetically Modified / genetics
  • Animals, Genetically Modified / metabolism
  • Antagomirs / metabolism
  • Base Sequence
  • Cell Differentiation
  • Cells, Cultured
  • Insulin-Like Growth Factor II / genetics
  • Insulin-Like Growth Factor II / metabolism*
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Muscle Development / genetics*
  • MyoD Protein / metabolism
  • Myoblasts / cytology
  • Myoblasts / metabolism
  • Myoglobin / metabolism
  • RNA Interference
  • RNA, Long Noncoding / antagonists & inhibitors
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • RNA, Small Interfering / metabolism
  • Sequence Alignment
  • Sheep

Substances

  • 3' Untranslated Regions
  • Antagomirs
  • MicroRNAs
  • MyoD Protein
  • Myoglobin
  • RNA, Long Noncoding
  • RNA, Small Interfering
  • Insulin-Like Growth Factor II