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Structure of Musashi1 in a complex with target RNA: the role of aromatic stacking interactions

Mammalian Musashi1 (Msi1) is an RNA-binding protein that regulates the translation of target mRNAs, and participates in the maintenance of cell ‘stemness’ and tumorigenesis. Msi1 reportedly binds to the 3′-untranslated region of mRNA of Numb, which encodes Notch inhibitor, and impedes initiation of...

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Autores principales: Ohyama, Takako, Nagata, Takashi, Tsuda, Kengo, Kobayashi, Naohiro, Imai, Takao, Okano, Hideyuki, Yamazaki, Toshio, Katahira, Masato
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3326303/
https://www.ncbi.nlm.nih.gov/pubmed/22140116
http://dx.doi.org/10.1093/nar/gkr1139
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author Ohyama, Takako
Nagata, Takashi
Tsuda, Kengo
Kobayashi, Naohiro
Imai, Takao
Okano, Hideyuki
Yamazaki, Toshio
Katahira, Masato
author_facet Ohyama, Takako
Nagata, Takashi
Tsuda, Kengo
Kobayashi, Naohiro
Imai, Takao
Okano, Hideyuki
Yamazaki, Toshio
Katahira, Masato
author_sort Ohyama, Takako
collection PubMed
description Mammalian Musashi1 (Msi1) is an RNA-binding protein that regulates the translation of target mRNAs, and participates in the maintenance of cell ‘stemness’ and tumorigenesis. Msi1 reportedly binds to the 3′-untranslated region of mRNA of Numb, which encodes Notch inhibitor, and impedes initiation of its translation by competing with eIF4G for PABP binding, resulting in triggering of Notch signaling. Here, the mechanism by which Msi1 recognizes the target RNA sequence using its Ribonucleoprotein (RNP)-type RNA-binding domains (RBDs), RBD1 and RBD2 has been revealed on identification of the minimal binding RNA for each RBD and determination of the three-dimensional structure of the RBD1:RNA complex. Unique interactions were found for the recognition of the target sequence by Msi1 RBD1: adenine is sandwiched by two phenylalanines and guanine is stacked on the tryptophan in the loop between β1 and α1. The minimal recognition sequences that we have defined for Msi1 RBD1 and RBD2 have actually been found in many Msi1 target mRNAs reported to date. The present study provides molecular clues for understanding the biology involving Musashi family proteins.
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spelling pubmed-33263032012-04-16 Structure of Musashi1 in a complex with target RNA: the role of aromatic stacking interactions Ohyama, Takako Nagata, Takashi Tsuda, Kengo Kobayashi, Naohiro Imai, Takao Okano, Hideyuki Yamazaki, Toshio Katahira, Masato Nucleic Acids Res Structural Biology Mammalian Musashi1 (Msi1) is an RNA-binding protein that regulates the translation of target mRNAs, and participates in the maintenance of cell ‘stemness’ and tumorigenesis. Msi1 reportedly binds to the 3′-untranslated region of mRNA of Numb, which encodes Notch inhibitor, and impedes initiation of its translation by competing with eIF4G for PABP binding, resulting in triggering of Notch signaling. Here, the mechanism by which Msi1 recognizes the target RNA sequence using its Ribonucleoprotein (RNP)-type RNA-binding domains (RBDs), RBD1 and RBD2 has been revealed on identification of the minimal binding RNA for each RBD and determination of the three-dimensional structure of the RBD1:RNA complex. Unique interactions were found for the recognition of the target sequence by Msi1 RBD1: adenine is sandwiched by two phenylalanines and guanine is stacked on the tryptophan in the loop between β1 and α1. The minimal recognition sequences that we have defined for Msi1 RBD1 and RBD2 have actually been found in many Msi1 target mRNAs reported to date. The present study provides molecular clues for understanding the biology involving Musashi family proteins. Oxford University Press 2012-04 2011-12-02 /pmc/articles/PMC3326303/ /pubmed/22140116 http://dx.doi.org/10.1093/nar/gkr1139 Text en © The Author(s) 2011. 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 Structural Biology
Ohyama, Takako
Nagata, Takashi
Tsuda, Kengo
Kobayashi, Naohiro
Imai, Takao
Okano, Hideyuki
Yamazaki, Toshio
Katahira, Masato
Structure of Musashi1 in a complex with target RNA: the role of aromatic stacking interactions
title Structure of Musashi1 in a complex with target RNA: the role of aromatic stacking interactions
title_full Structure of Musashi1 in a complex with target RNA: the role of aromatic stacking interactions
title_fullStr Structure of Musashi1 in a complex with target RNA: the role of aromatic stacking interactions
title_full_unstemmed Structure of Musashi1 in a complex with target RNA: the role of aromatic stacking interactions
title_short Structure of Musashi1 in a complex with target RNA: the role of aromatic stacking interactions
title_sort structure of musashi1 in a complex with target rna: the role of aromatic stacking interactions
topic Structural Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3326303/
https://www.ncbi.nlm.nih.gov/pubmed/22140116
http://dx.doi.org/10.1093/nar/gkr1139
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