Overview of microRNA biology

Abstract

In considering an overview of microRNA biology, it is useful to consider microRNAs as a part of cellular communication. At the simplest level, microRNAs act to decrease the expression of messenger RNAs that contain stretches of sequence complementary to the microRNA. This function can be likened to the function of endogenous or synthetic short interfering RNA. However, microRNA function is more complicated and nuanced than this "on-off" model would suggest. Further, many microRNA targets are themselves noncoding RNAs. In this review, the authors discuss the role of microRNAs in shaping the proteome of the cell in a way that is consistent with microRNA involvement in a highly regulated conversation, sensitive to outside influence and internal feedback.

Figure 1. MicroRNAs as biomarkers and prognostic factors

MicroRNAs are secreted into various bodily fluids which can be altered by disease states. Current studies are attempting to utilize microRNAs in these fluids for diagnostic and prognostic value. Examples are listed in this diagram: cerebrospinal fluid, Alzheimer’s disease; vitreous humor, ocular diseases; saliva, esophageal cancer; blood, cardiovascular disease; bile, cholangiocarcinoma; gastric juice, gastric cancer; pancreatic juice, pancreatic cancer; urine, renal fibrosis; fecal matter, colon cancer; synovial fluid, Rheumatoid arthritis.

Figure 2. Alternative microRNA targeting

Multiple instances may arise in which microRNAs can no longer bind to their intended targets. Three examples are: 1) Alternative splicing - the microRNA binding site is spliced out of the target transcript; 2) Alternative polyadenylation signals - short 3′UTRs lack the microRNA binding site; and 3) Single nucleotide polymorphisms - altered microRNA binding sequence in the target mRNA inhibiting binding site recognition.

Figure 3. MicroRNA-microRNA binding

Mature microRNAs can bind in a sequence-specific manner to each other, as demonstrated by cross-linking, ligation and sequencing of hybrids (CLASH). Illustrated here is the antiparallel microRNA duplex containing let-7a and miR-30c, adapted from Helwak et al., 2013. The 5′ terminus and seed region of each microRNA is indicated in yellow (nucleotides 1-8) and the remaining microRNA is in grey. Vertical ‘ladder rungs’ indicate Watson-Crick base pairing, while the absence of a rung indicates a mismatch (i.e., within the miR-30c seed). Single nucleotide bulges (either symmetric or asymmetric) are depicted as a triangular deviation of the backbone.