miRNAs are small non-coding RNAs that regulate post-transcriptionally gene expression by degradation or translational repression
of specific target mRNAs. In the 90s, lin-4 and let-7 were firstly identified as small regulatory RNAs able to control C. elegans
larval development, by specifically targeting the 3’UTR of lin-14 and lin-28, respectively. These findings have introduced a novel and
wide layer of complexity in the regulation of mRNA and protein expression. Lin-4 and let-7 are now considered the founding members of
an abundant class of small fine-tuned RNAs, called microRNAs (miRNAs), in viruses, green algae, plants, flies, worms, and in mammals.
In humans, the estimated number of genes encoding for miRNAs is as high as 1000 and around 30% of the protein-coding genes
are post-transcriptionally controlled by miRNAs.
This article reviews the role of miRNAs in regulating several biological responses in muscle cells, ranging from proliferation, differentiation
and adaptation to stress cues. Cardiac and skeletal muscles are powerful examples to summarize the activity of miRNAs in cell fate
specification, lineage differentiation and metabolic pathways. Indeed, specific miRNAs control the number of proliferating muscle progenitors
to guarantee the proper formation of the heart and muscle fibers and to assure the self-renewal of muscle progenitors during
adult tissue regeneration. On the other side, several other miRNAs promote the differentiation of muscle progenitors into skeletal myofibers
or into cardiomyocytes, where metabolic activity, survival and remodeling process in response to stress, injury and chronic diseases
are also fine-tuned by miRNAs.