MicroRNA, Cell Fate Maintenance, and Aging
From Santa Fe Institute Event Wiki
MicroRNAs (miRNAs), a class of small RNAs of ~22 base pairs, function as silencers to suppress gene expression post-transcriptionally, either by degrading the messages or by inhibiting translation via binding at the 3’-untranslated region (UTR). Individual miRNA species may target hundreds of genes; vice versa, individual genes may be repressed by multiple miRNAs. This molecular design allows maximal flexibility in the implementation of signaling events directing every cellular function, but creates a challenge to deciphering the temporal and spatial control of how these natural, small RNA molecules function and operate. Conceptually, microRNAs may be most important in cell lineage determination, functioning as key modulators at every bifurcation point to direct the fate of individual cell types. For example, post-mitotic cells such as neurons and cardiomyocytes must remain long-term in a permanent growth arrest state, necessitating sharing certain miRNAs which target silencing the expression of cell cycle traverse genes. Thus, miRNAs may be separated into at least two categories, Case 1 containing those determining the fate of major cell types, and Case 2 consisting of those controlling specific signaling events within individual cells. Individual miRNA species, acting either as Case 1, Case 2 or both, may then dictate the signaling network of gene expressions needed for a particular cellular function. An obvious question raised here is whether aging may in part be attributed to malfunctioning or gradual erosion of specific miRNAs’ operation to control the fate of unique tissue niches. Thus, programmatic ‘misfires’ at the individual miRNA operational level may eventually culminate in age-dependent, tissue-wide compromise, such as a reduced rate of wound healing, etc. The challenge for system biology is then to understand how these ‘misfires’ occur, and how they initiate the erosion of cell fate maintenance during aging, ultimately leading to age-dependent frailty and diseases.
