Providing possible therapeutic targets to delay muscle atrophy and death

Skeletal muscle is the largest tissue in the body and serves as its biggest reservoir of amino acids. During development, and following exercise, muscles can undergo hypertrophy resulting in increased mass, while starvation and certain disorders can result in a net loss of muscle protein, a condition known as atrophy. Some of the conditions that lead to atrophy include: diabetes, cancer cachexia, motor neuron diseases, spinal cord injury, immobility, and aging.

The underlying molecular mechanisms of muscular atrophy and death are poorly understood, which hinders the development of therapeutic targets to delay muscle atrophy and death. MicroRNAs (miRs), are small (~22 nucleotide) non-coding RNAs that bind to sequences in messenger RNAs (mRNAs) and regulate transcript stability and translatability. Partial complementarity between the miRs and mRNAs results in translational arrest while complete complementarity results in mRNA degradation.

The intersegmental muscles (ISMs) of the tobacco hawkmoth Manduca sexta undergo muscular atrophy rapidly making it a fundamental model system to study muscular atrophy and death in vivo. By showing that miRs play a role in posttranscriptional regulation by controlling the stability and or translatability of target mRNAs in the ISMs, the molecular mechanisms underlying muscular atrophy and death can be better understood, and possible targets to delay or even prevent muscle atrophy and death can be discovered.