Regulation of senescence by microRNA biogenesis factors.

Senescence represents a state of indefinite growth arrest in cells that have reached the end of their replicative life span, have become damaged, or express aberrant levels of cancer-related proteins. While senescence is widely considered to represent a tumor-suppressive mechanism, the accumulation of senescent cells in tissues of older organisms is believed to underlie age-associated losses in physiologic function and age-related diseases. With the emergence of microRNAs (miRNAs) as a major class of molecular regulators of senescence, we review the transcriptional and post-transcriptional factors that control senescence-associated microRNA biosynthesis. Focusing on their enhancement or repression of senescence, we describe the transcription factors that govern the synthesis of primary (pri-)miRNAs, the proteins that control the nuclear processing of pri-miRNAs into precursor (pre-)miRNAs, including RNA editing enzymes, RNases, and RNA helicases, and the cytoplasmic proteins that affect the final processing of pre-miRNAs into mature miRNAs. We discuss how miRNA biogenesis proteins promote or inhibit senescence, and thus influence the senescent phenotype that affects normal tissue function and pathology. Published by Elsevier B.V.