Caenorhabditis elegans ALG-1 antimorphic mutations uncover functions for Argonaute in microRNA guide strand selection and passenger strand disposal
Abstract
Significance: Loading of Argonautes with the correct strand of the pre-miRNA duplex and disposal of the other strand are essential steps in microRNA biogenesis. Here we report characterization of the protein and microRNA populations associated with mutant ALG-1 Argonautes that are defective in transitioning from microRNA processing to target repression. We show that mutant Argonaute erroneously associates with the normally discarded microRNA* strands, signifying a role for Argonaute ALG-1 in microRNA strand selection. Accumulation of microRNA* is dependent on the microRNA identity, suggesting that specific microRNA features allow wild-type Argonautes to distinguish among different microRNAs. These findings are relevant to understanding Argonaute roles in microRNA biogenesis and, more broadly, to the functions of microRNAs in development and disease.
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In C. elegans, single amino acid substitutions within the MID (G553R) and PIWI (G716E, S895F, and S939F) domains of the miRNA Argonaute ALG-1 reverse the strand selection of certain miRNAs.
“Consistently, in C. elegans, single amino acid substitutions within the MID (G553R) and PIWI (G716E, S895F, and S939F) domains of the miRNA Argonaute ALG‐1 (Argonaute‐like Gene) reverse the strand selection of certain miRNAs (Zinovyeva, Bouasker, Simard, Hammell, & Ambros, 2014; Zinovyeva, Veksler‐Lublinsky, Vashisht, Wohlschlegel, & Ambros, 2015).”
From microRNA strand selection: Unwinding the rules (2021) · cites this paper as Zinovyeva et al., 2015
ALG-1 mutations that affect strand selection do not reverse strand selection for all miRNAs, suggesting that additional intrinsic or extrinsic factors may affect C. elegans miRNA strand selection differently for distinct miRNAs.
“Interestingly, these ALG‐1 mutations do not reverse strand selection for all miRNAs, suggesting that additional intrinsic or extrinsic factors may affect C. elegans miRNA strand selection differently for distinct miRNAs (Zinovyeva et al., 2015).”
From microRNA strand selection: Unwinding the rules (2021) · cites this paper as Zinovyeva et al., 2015
Obvious miRNA duplex-intrinsic factors, such as 5' nt identity or end stability, were not able to distinguish the strand switching-miRNAs from miRNAs resistant to ALG-1 mutations.
“Obvious miRNA duplex‐intrinsic factors, such as 5′ nt identity or end stability, were not able to distinguish the strand switching‐miRNAs from miRNAs resistant to ALG‐1 mutations (Zinovyeva et al., 2015).”
From microRNA strand selection: Unwinding the rules (2021) · cites this paper as Zinovyeva et al., 2015
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Cites
A Mammalian microRNA Expression Atlas Based on Small RNA Library Sequencing
Landgraf, P., Rusu, M., Sheridan, R., Sewer, A., Iovino, N., Aravin, A., Pfeffer, S., Rice, A., Kamphorst, A. O., Landthaler, M., et al. (2007) · Cell · doi:10.1016/j.cell.2007.04.040 · Cited by 3,626 · see citing works
Small-RNA asymmetry is directly driven by mammalian Argonautes
Suzuki, H. I., Katsura, A., Yasuda, T., Ueno, T., Mano, H., Sugimoto, K., & Miyazono, K. (2015) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.3050 · Cited by 108 · cited 1× · see citing works
“Indeed, a very recent report has suggested a direct role for mAGO2 in miR strand choice (30).”
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Research works printed but not linked: 3
- [54]Cociorva D, Tabb DL, Yates JR (2006) Validation of tandem mass spectrometry data- base search results using DTASelect. Curr Protoc Bioinformatics Chapter 13:Unit 4.
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microRNA strand selection: Unwinding the rules
Medley, J. C., Panzade, G., & Zinovyeva, A. Y. (2021) · WIREs RNA · doi:10.1002/wrna.1627 · Cited by 225 · see citing works
Self-citation
- Authors
- Zinovyeva, A. Y., Veksler-Lublinsky, I., Vashisht, A. A., Wohlschlegel, J. A., & Ambros, V. R.
- Affiliations
- Program in Molecular Medicine, RNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, MA 01605;
- Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles, CA 90095
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2015-09-08
- Volume
- 112
- Issue
- 38
- ISSN
- 0027-8424
- 1091-6490
- Cited by
- 35
- References
- 2
- Language
- en
- Funders
- HHS | NIH | National Institute of General Medical Sciences (R01GM34028, R01GM089778)
- Leukemia and Lymphoma Society (5354-15)
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