MicroRNA-34/449 family and viral infections

Highlights • Origin and genomic organization of the miR-34/449 family in vertebrates. • Expression of the mir-34/449 family regulated by viral infection. • Virus replication regulated by the mir-34/449 family. • Inflammatory responses regulated by the miR-34/449 family after viral infection.
MicroRNAs are short, endogenous, nonprotein-coding RNAs that are essential for regulation of cellular processes through gene silencing. The miR-34/449 family is conserved in mammalian organisms and generally comprises six homologous genes: miR-34a, miR-34b, miR-34c, miR-449a, miR-449b and miR-449c, at three genomic loci. Strong similarity in the sequence of these miRNAs, particularly at the seed region, predicts robust functional redundancy. A large proportion of the literature on the miR-34/449 family focuses on its role in regulating cell cycle arrest and apoptosis by modulating E2F- and p53-related signaling pathways. A growing subset of the literature reports that the miR-34/449 family is involved in the regulation of immune responses and viral infections, and data suggest the potential for miR-34/446 as a diagnostic and therapeutic target. In this review, we discuss our current understanding of the conservation and transcriptional regulation of the miR-34/449 family and review the literature on its functions in viral infections.