MicroRNA-351 inhibits denervation-induced muscle atrophy by targeting TRAF6

Qianru He1, Jiaying Qiu1, Ming Dai2

  • 1Jiangsu Key Laboratory of Neuroregeneration, Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu 226001, P.R. China.

Insights

MicroRNAs (miRs) regulate muscle mass. This study found that miR-351 inhibits muscle atrophy after nerve injury by targeting TRAF6, MuRF1, and MAFBx, preserving muscle size and function.

Area of Science:

  • Molecular Biology
  • Muscle Physiology
  • Biochemistry

Background:

  • MicroRNAs (miRs) are implicated in various physiological and pathological processes.
  • The role of miRs in muscle atrophy, particularly following nerve injury, remains incompletely understood.

Purpose of the Study:

  • To investigate the role of miR-351 in denervation-induced muscle atrophy.
  • To identify the molecular targets and mechanisms through which miR-351 modulates muscle atrophy.

Main Methods:

  • Sciatic nerve transection model in tibialis anterior (TA) muscle.
  • Quantitative real-time PCR and Western blot analysis for gene and protein expression.
  • Dual luciferase reporter assay to confirm direct targeting.
  • Assessment of muscle weight and cross-sectional area.

Main Results:

  • miR-351 expression was inversely correlated with TRAF6 (Tumor Necrosis Factor Receptor-Associated Factor 6) mRNA and protein levels post-nerve injury.
  • miR-351 directly targeted the 3'-untranslated region of TRAF6, downregulating its expression.
  • Overexpression of miR-351 attenuated denervation-induced reductions in TA muscle weight and cross-sectional area.
  • miR-351 overexpression suppressed the protein levels of TRAF6, MuRF1 (Muscle Ring-Finger Protein 1), and MAFBx (Muscle Atrophy F-box) in denervated muscle.

Conclusions:

  • miR-351 plays a protective role against denervation-induced muscle atrophy in the tibialis anterior muscle.
  • This protective effect is mediated, at least partly, by the negative regulation of TRAF6 and its downstream targets, MuRF1 and MAFBx.

Related Concept Videos

MicroRNAs01:22

MicroRNAs

MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between genes). Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself, forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA...
4.2K
MicroRNAs01:22

MicroRNAs

MicroRNA (miRNA) are short, regulatory RNA transcribed from introns—non-coding regions of a gene—or intergenic regions—stretches of DNA present between genes. Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After...
24.5K
Directly Acting Muscle Relaxants: Dantrolene and Botulinum Toxin01:26

Directly Acting Muscle Relaxants: Dantrolene and Botulinum Toxin

Directly acting muscle relaxants like dantrolene and botulinum toxin (BoNT) have distinct mechanisms and applications. Dantrolene, a hydantoin derivative, acts on the ryanodine receptor (RYR1) in skeletal muscle cells. RYR1 are calcium channels present at the sarcoplasmic reticulum membrane. In response to excitation, they release calcium ions from the sarcoplasmic reticulum to the cytosol. Calcium promotes actin-myosin-mediated contraction of muscles.
The binding of dantrolene to the RYR1...
1.3K