Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2019:84:179-183.
doi: 10.1101/sqb.2019.84.039321. Epub 2020 Feb 4.

How Complementary Targets Expose the microRNA 3' End for Tailing and Trimming during Target-Directed microRNA Degradation

Paulina Pawlica  1 , Jessica Sheu-Gruttadauria  2 , Ian J MacRae  2 , Joan A Steitz  1
Affiliations

How Complementary Targets Expose the microRNA 3' End for Tailing and Trimming during Target-Directed microRNA Degradation

Paulina Pawlica et al. Cold Spring Harb Symp Quant Biol. 2019.

Abstract

microRNAs (miRNAs) are crucial for posttranscriptional regulation of messenger RNAs. "Classical" miRNA targets predominantly interact with the miRNA seed sequence located near the miRNA 5' end. Interestingly, certain transcripts that exhibit extensive complementarity to the miRNAs 3' region, instead of being subjected to regulation, induce miRNA decay in a process termed target-directed miRNA degradation (TDMD). Here, we review recent advances in understanding the molecular mechanisms of TDMD. Specifically, we discuss how extensive miRNA complementarity to TDMD-inducing targets results in displacement of the miRNA 3' end from its protective pocket in the Argonaute protein. Unprotected miRNA 3' ends are then available for enzymatic attack by still-unidentified cellular enzymes. Identification of these cellular enzymes and discovery of additional TDMD-inducing transcripts are subjects for future research.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
Three known modes of miRNA-target interaction on Ago proteins result in different outcomes.
Figure 2.
Figure 2.
Binding of a TDMD target exposes the miRNA 3′ end. Crystal structures of the Ago2-miRNA complex bound to a “classical” miRNA target with seed+supplementary pairing (left, PDB 6N4O) or a TDMD-inducing target RNA (right, PDB 6MDZ). Insets show close-up views of the miRNA 3′ end bound to the PAZ domain in the seed+supplementary structure or exposed to enzymatic attack in the TDMD conformation. Below, observed miRNA-target base pairs are shown schematically.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Ameres SL, Horwich MD, Hung JH, Xu J, Ghildiyal M, Weng Z, Zamore PD. 2010. Target RNA-directed trimming and tailing of small silencing RNAs. Science 328: 1534–1539. - PMC - PubMed
    1. Astrom J, Astrom A, Virtanen A. 1992. Properties of a HeLa cell 3’ exonuclease specific for degrading poly(A) tails of mammalian mRNA. The Journal of biological chemistry 267: 18154–18159. - PubMed
    1. Baccarini A, Chauhan H, Gardner TJ, Jayaprakash AD, Sachidanandam R, Brown BD. 2011. Kinetic analysis reveals the fate of a microRNA following target regulation in mammalian cells. Current biology : CB 21: 369–376. - PMC - PubMed
    1. Bartel DP. 2018. Metazoan microRNAs. Cell 173: 20–51. - PMC - PubMed
    1. Bitetti A, Mallory AC, Golini E, Carrieri C, Carreno Gutierrez H, Perlas E, Perez-Rico YA, Tocchini-Valentini GP, Enright AJ, Norton WHJ, Mandillo S, O’Carroll D, Shkumatava A. 2018. MicroRNA degradation by a conserved target RNA regulates animal behavior. Nat Struct Mol Biol 25: 244–251. - PubMed

LinkOut - more resources