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Argonaute identity defines the length of mature mammalian microRNAs

MicroRNAs (miRNAs) are 19- to 25-nt-long non-coding RNAs that regulate gene expression by base-pairing with target mRNAs and reducing their stability or translational efficiency. Mammalian miRNAs function in association with four closely related Argonaute proteins, AGO1–4. All four proteins contain...

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Autores principales: Juvvuna, Prasanna Kumar, Khandelia, Piyush, Lee, Li Ming, Makeyev, Eugene V.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2012
Materias:
RNA
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3413106/
https://www.ncbi.nlm.nih.gov/pubmed/22505576
http://dx.doi.org/10.1093/nar/gks293
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author Juvvuna, Prasanna Kumar
Khandelia, Piyush
Lee, Li Ming
Makeyev, Eugene V.
author_facet Juvvuna, Prasanna Kumar
Khandelia, Piyush
Lee, Li Ming
Makeyev, Eugene V.
author_sort Juvvuna, Prasanna Kumar
collection PubMed
description MicroRNAs (miRNAs) are 19- to 25-nt-long non-coding RNAs that regulate gene expression by base-pairing with target mRNAs and reducing their stability or translational efficiency. Mammalian miRNAs function in association with four closely related Argonaute proteins, AGO1–4. All four proteins contain the PAZ and the MID domains interacting with the miRNA 3′ and 5′ termini, respectively, as well as the PIWI domain comprising an mRNA ‘slicing’ activity in the case of AGO2 but not AGO1, AGO3 and AGO4. However, the slicing mode of the miRNA-programmed AGO2 is rarely realized in vivo and the four Argonautes are thought to play largely overlapping roles in the mammalian miRNA pathway. Here, we show that the average length of many miRNAs is diminished during nervous system development as a result of progressive shortening of the miRNA 3′ ends. We link this modification with an increase in the fractional abundance of Ago2 in the adult brain and identify a specific structural motif within the PAZ domain that enables efficient trimming of miRNAs associated with this but not the other three Argonautes. Taken together, our data suggest that mammalian Argonautes may define the length and possibly biological activity of mature mammalian miRNAs in a developmentally controlled manner.
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spelling pubmed-34131062012-08-07 Argonaute identity defines the length of mature mammalian microRNAs Juvvuna, Prasanna Kumar Khandelia, Piyush Lee, Li Ming Makeyev, Eugene V. Nucleic Acids Res RNA MicroRNAs (miRNAs) are 19- to 25-nt-long non-coding RNAs that regulate gene expression by base-pairing with target mRNAs and reducing their stability or translational efficiency. Mammalian miRNAs function in association with four closely related Argonaute proteins, AGO1–4. All four proteins contain the PAZ and the MID domains interacting with the miRNA 3′ and 5′ termini, respectively, as well as the PIWI domain comprising an mRNA ‘slicing’ activity in the case of AGO2 but not AGO1, AGO3 and AGO4. However, the slicing mode of the miRNA-programmed AGO2 is rarely realized in vivo and the four Argonautes are thought to play largely overlapping roles in the mammalian miRNA pathway. Here, we show that the average length of many miRNAs is diminished during nervous system development as a result of progressive shortening of the miRNA 3′ ends. We link this modification with an increase in the fractional abundance of Ago2 in the adult brain and identify a specific structural motif within the PAZ domain that enables efficient trimming of miRNAs associated with this but not the other three Argonautes. Taken together, our data suggest that mammalian Argonautes may define the length and possibly biological activity of mature mammalian miRNAs in a developmentally controlled manner. Oxford University Press 2012-08 2012-04-13 /pmc/articles/PMC3413106/ /pubmed/22505576 http://dx.doi.org/10.1093/nar/gks293 Text en © The Author(s) 2012. Published by Oxford University Press. http://creativecommons.org/licenses/by-nc/3.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle RNA
Juvvuna, Prasanna Kumar
Khandelia, Piyush
Lee, Li Ming
Makeyev, Eugene V.
Argonaute identity defines the length of mature mammalian microRNAs
title Argonaute identity defines the length of mature mammalian microRNAs
title_full Argonaute identity defines the length of mature mammalian microRNAs
title_fullStr Argonaute identity defines the length of mature mammalian microRNAs
title_full_unstemmed Argonaute identity defines the length of mature mammalian microRNAs
title_short Argonaute identity defines the length of mature mammalian microRNAs
title_sort argonaute identity defines the length of mature mammalian micrornas
topic RNA
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3413106/
https://www.ncbi.nlm.nih.gov/pubmed/22505576
http://dx.doi.org/10.1093/nar/gks293
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