Ménage à Trois
Intimate Relationship Among a MicroRNA, Long Noncoding RNA, and mRNA
“A disaster of biblical proportions....Dogs and cats living together! Mass hysteria!”
—Bill Murray as Dr Peter Venkman in the 1984 film Ghostbusters, cowritten by the late Harold Ramis and Dan Aykroyd
The idea that cross-species cohabitation is catastrophic does not seem to apply to RNA. Post-transcriptional regulation of protein-coding mRNA transcripts bound by ≈20-nucleotide single-stranded microRNAs is thoroughly established.1 Another species of noncoding RNA, designated as long noncoding (lnc) RNAs because of their longer size (>200 nucleotides), can regulate microRNA abundance by binding and sequestering them, acting as so-called microRNA sponges.2 In this issue of Circulation Research, Wang et al3 close the circle by describing a lncRNA–microRNA–mRNA trio that functions interdependently to regulate cardiac hypertrophy. The mRNA encodes the immune response adaptor protein Myd88 (myeloid differentiation primary response 88), which regulates cardiomyocyte and cardiac hypertrophy via mechanisms that are not defined. Myd88 can be targeted by microRNA-489 (miR-489), steady-state levels of which are decreased during angiotensin II–stimulated cardiomyocyte hypertrophy (thus derepressing Myd88). And, miR-489 can also be bound by lncRNA AK048451 (here named cardiac hypertrophy–related factor), levels of which are increased by angiotensin II; by sequestering miR-489, cardiac hypertrophy–related factor impairs the ability of microRNA to downregulate Myd88 mRNA.
Article, see p 1377
One of the revelations of multispecies genome sequencing is that organism complexity relates to the richness of the genetic regulatory machinery, not the number of protein-coding genes. Much of the noncoding mammalian genome previously referred to as junk DNA is now recognized as regulatory. For example, conventional DNA-binding transactivating proteins4 work in concert with microRNAs to orchestrate development of embryonic hearts and the response to cardiac stress.1
MicroRNAs are one of multiple species of noncoding RNAs that also include lncRNAs. Because RNAs do not possess intrinsic catalytic activity, biological function …