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Structural insights into a unique preference for 3′ terminal guanine of mirtron in Drosophila TUTase tailor

Terminal uridylyl transferase (TUTase) is one type of enzyme that modifies RNA molecules by facilitating the post-transcriptional addition of uridyl ribonucleotides to their 3′ ends. Recent researches have reported that Drosophila TUTase, Tailor, exhibits an intrinsic preference for RNA substrates e...

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Autores principales: Cheng, Lin, Li, Fudong, Jiang, Yiyang, Yu, Hailong, Xie, Changlin, Shi, Yunyu, Gong, Qingguo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6326804/
https://www.ncbi.nlm.nih.gov/pubmed/30407553
http://dx.doi.org/10.1093/nar/gky1116
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author Cheng, Lin
Li, Fudong
Jiang, Yiyang
Yu, Hailong
Xie, Changlin
Shi, Yunyu
Gong, Qingguo
author_facet Cheng, Lin
Li, Fudong
Jiang, Yiyang
Yu, Hailong
Xie, Changlin
Shi, Yunyu
Gong, Qingguo
author_sort Cheng, Lin
collection PubMed
description Terminal uridylyl transferase (TUTase) is one type of enzyme that modifies RNA molecules by facilitating the post-transcriptional addition of uridyl ribonucleotides to their 3′ ends. Recent researches have reported that Drosophila TUTase, Tailor, exhibits an intrinsic preference for RNA substrates ending in 3′G, distinguishing it from any other known TUTases. Through this unique feature, Tailor plays a crucial role as the repressor in the biogenesis pathway of splicing-derived mirtron pre-miRNAs. Here we describe crystal structures of core catalytic domain of Tailor and its complexes with RNA stretches 5′-AGU-3′ and 5′-AGUU-3′. We demonstrate that R327 and N347 are two key residues contributing cooperatively to Tailor's preference for 3′G, and R327 may play an extra role in facilitating the extension of polyuridylation chain. We also demonstrate that conformational stability of the exit of RNA-binding groove also contributes significantly to Tailor's activity. Overall, our work reveals useful insights to explain why Drosophila Tailor can preferentially select RNA substrates ending in 3′G and provides important values for further understanding the biological significances of biogenesis pathway of mirtron in flies.
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spelling pubmed-63268042019-01-15 Structural insights into a unique preference for 3′ terminal guanine of mirtron in Drosophila TUTase tailor Cheng, Lin Li, Fudong Jiang, Yiyang Yu, Hailong Xie, Changlin Shi, Yunyu Gong, Qingguo Nucleic Acids Res Structural Biology Terminal uridylyl transferase (TUTase) is one type of enzyme that modifies RNA molecules by facilitating the post-transcriptional addition of uridyl ribonucleotides to their 3′ ends. Recent researches have reported that Drosophila TUTase, Tailor, exhibits an intrinsic preference for RNA substrates ending in 3′G, distinguishing it from any other known TUTases. Through this unique feature, Tailor plays a crucial role as the repressor in the biogenesis pathway of splicing-derived mirtron pre-miRNAs. Here we describe crystal structures of core catalytic domain of Tailor and its complexes with RNA stretches 5′-AGU-3′ and 5′-AGUU-3′. We demonstrate that R327 and N347 are two key residues contributing cooperatively to Tailor's preference for 3′G, and R327 may play an extra role in facilitating the extension of polyuridylation chain. We also demonstrate that conformational stability of the exit of RNA-binding groove also contributes significantly to Tailor's activity. Overall, our work reveals useful insights to explain why Drosophila Tailor can preferentially select RNA substrates ending in 3′G and provides important values for further understanding the biological significances of biogenesis pathway of mirtron in flies. Oxford University Press 2019-01-10 2018-11-08 /pmc/articles/PMC6326804/ /pubmed/30407553 http://dx.doi.org/10.1093/nar/gky1116 Text en © The Author(s) 2018. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Structural Biology
Cheng, Lin
Li, Fudong
Jiang, Yiyang
Yu, Hailong
Xie, Changlin
Shi, Yunyu
Gong, Qingguo
Structural insights into a unique preference for 3′ terminal guanine of mirtron in Drosophila TUTase tailor
title Structural insights into a unique preference for 3′ terminal guanine of mirtron in Drosophila TUTase tailor
title_full Structural insights into a unique preference for 3′ terminal guanine of mirtron in Drosophila TUTase tailor
title_fullStr Structural insights into a unique preference for 3′ terminal guanine of mirtron in Drosophila TUTase tailor
title_full_unstemmed Structural insights into a unique preference for 3′ terminal guanine of mirtron in Drosophila TUTase tailor
title_short Structural insights into a unique preference for 3′ terminal guanine of mirtron in Drosophila TUTase tailor
title_sort structural insights into a unique preference for 3′ terminal guanine of mirtron in drosophila tutase tailor
topic Structural Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6326804/
https://www.ncbi.nlm.nih.gov/pubmed/30407553
http://dx.doi.org/10.1093/nar/gky1116
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