Fine-Tuning of mTOR mRNA and Nucleolin Complexes by SMN

Increasing evidence points to the Survival Motor Neuron (SMN) protein as a key determinant of translation pathway. Besides its role in RNA processing and sorting, several works support a critical implication of SMN in ribosome biogenesis. We previously showed that SMN binds ribosomal proteins (RPs)...

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Main Authors: Francesca Gabanella, Christian Barbato, Marco Fiore, Carla Petrella, Marco de Vincentiis, Antonio Greco, Antonio Minni, Nicoletta Corbi, Claudio Passananti, Maria Grazia Di Certo
Format: Article
Language:English
Published: MDPI AG 2021-11-01
Series:Cells
Subjects:
Online Access:https://www.mdpi.com/2073-4409/10/11/3015
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author Francesca Gabanella
Christian Barbato
Marco Fiore
Carla Petrella
Marco de Vincentiis
Antonio Greco
Antonio Minni
Nicoletta Corbi
Claudio Passananti
Maria Grazia Di Certo
author_facet Francesca Gabanella
Christian Barbato
Marco Fiore
Carla Petrella
Marco de Vincentiis
Antonio Greco
Antonio Minni
Nicoletta Corbi
Claudio Passananti
Maria Grazia Di Certo
author_sort Francesca Gabanella
collection DOAJ
description Increasing evidence points to the Survival Motor Neuron (SMN) protein as a key determinant of translation pathway. Besides its role in RNA processing and sorting, several works support a critical implication of SMN in ribosome biogenesis. We previously showed that SMN binds ribosomal proteins (RPs) as well as their encoding transcripts, ensuring an appropriate level of locally synthesized RPs. SMN impacts the translation machinery in both neural and non-neural cells, in agreement with the concept that SMN is an essential protein in all cell types. Here, we further assessed the relationship between SMN and translation-related factors in immortalized human fibroblasts. We focused on SMN-nucleolin interaction, keeping in mind that nucleolin is an RNA-binding protein, highly abundant within the nucleolus, that exhibits a central role in ribosomes production. Nucleolin may also affects translation network by binding the mammalian target of rapamycin (mTOR) mRNA and promoting its local synthesis. In this regard, for the first time we provided evidence that SMN protein itself associates with mTOR transcript. Collectively, we found that: (1) SMN coexists with nucleolin–mTOR mRNA complexes at subcellular level; (2) SMN deficiency impairs nucleolar compartmentalization of nucleolin, and (3) this event correlates with the nuclear retention of mTOR mRNA. These findings suggest that SMN may regulate not only structural components of translation machinery, but also their upstream regulating factors.
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spelling doaj.art-3f3840099b40440d9a1fd6e0a884ea452023-11-22T22:50:04ZengMDPI AGCells2073-44092021-11-011011301510.3390/cells10113015Fine-Tuning of mTOR mRNA and Nucleolin Complexes by SMNFrancesca Gabanella0Christian Barbato1Marco Fiore2Carla Petrella3Marco de Vincentiis4Antonio Greco5Antonio Minni6Nicoletta Corbi7Claudio Passananti8Maria Grazia Di Certo9CNR-Institute of Biochemistry and Cell Biology, Department of Sense Organs, Sapienza University of Rome, Viale del Policlinico, 155-00161 Rome, ItalyCNR-Institute of Biochemistry and Cell Biology, Department of Sense Organs, Sapienza University of Rome, Viale del Policlinico, 155-00161 Rome, ItalyCNR-Institute of Biochemistry and Cell Biology, Department of Sense Organs, Sapienza University of Rome, Viale del Policlinico, 155-00161 Rome, ItalyCNR-Institute of Biochemistry and Cell Biology, Department of Sense Organs, Sapienza University of Rome, Viale del Policlinico, 155-00161 Rome, ItalyDepartment of Sense Organs, Sapienza University of Rome, Viale del Policlinico, 155-00161 Rome, ItalyDepartment of Sense Organs, Sapienza University of Rome, Viale del Policlinico, 155-00161 Rome, ItalyDepartment of Sense Organs, Sapienza University of Rome, Viale del Policlinico, 155-00161 Rome, ItalyCNR-Institute of Molecular Biology and Pathology, Department of Molecular Medicine, Sapienza University of Rome, Viale Regina Elena, 291-00161 Rome, ItalyCNR-Institute of Molecular Biology and Pathology, Department of Molecular Medicine, Sapienza University of Rome, Viale Regina Elena, 291-00161 Rome, ItalyCNR-Institute of Biochemistry and Cell Biology, Department of Sense Organs, Sapienza University of Rome, Viale del Policlinico, 155-00161 Rome, ItalyIncreasing evidence points to the Survival Motor Neuron (SMN) protein as a key determinant of translation pathway. Besides its role in RNA processing and sorting, several works support a critical implication of SMN in ribosome biogenesis. We previously showed that SMN binds ribosomal proteins (RPs) as well as their encoding transcripts, ensuring an appropriate level of locally synthesized RPs. SMN impacts the translation machinery in both neural and non-neural cells, in agreement with the concept that SMN is an essential protein in all cell types. Here, we further assessed the relationship between SMN and translation-related factors in immortalized human fibroblasts. We focused on SMN-nucleolin interaction, keeping in mind that nucleolin is an RNA-binding protein, highly abundant within the nucleolus, that exhibits a central role in ribosomes production. Nucleolin may also affects translation network by binding the mammalian target of rapamycin (mTOR) mRNA and promoting its local synthesis. In this regard, for the first time we provided evidence that SMN protein itself associates with mTOR transcript. Collectively, we found that: (1) SMN coexists with nucleolin–mTOR mRNA complexes at subcellular level; (2) SMN deficiency impairs nucleolar compartmentalization of nucleolin, and (3) this event correlates with the nuclear retention of mTOR mRNA. These findings suggest that SMN may regulate not only structural components of translation machinery, but also their upstream regulating factors.https://www.mdpi.com/2073-4409/10/11/3015SMNnucleolinnucleolusribosome biogenesismTORRNA translation
spellingShingle Francesca Gabanella
Christian Barbato
Marco Fiore
Carla Petrella
Marco de Vincentiis
Antonio Greco
Antonio Minni
Nicoletta Corbi
Claudio Passananti
Maria Grazia Di Certo
Fine-Tuning of mTOR mRNA and Nucleolin Complexes by SMN
Cells
SMN
nucleolin
nucleolus
ribosome biogenesis
mTOR
RNA translation
title Fine-Tuning of mTOR mRNA and Nucleolin Complexes by SMN
title_full Fine-Tuning of mTOR mRNA and Nucleolin Complexes by SMN
title_fullStr Fine-Tuning of mTOR mRNA and Nucleolin Complexes by SMN
title_full_unstemmed Fine-Tuning of mTOR mRNA and Nucleolin Complexes by SMN
title_short Fine-Tuning of mTOR mRNA and Nucleolin Complexes by SMN
title_sort fine tuning of mtor mrna and nucleolin complexes by smn
topic SMN
nucleolin
nucleolus
ribosome biogenesis
mTOR
RNA translation
url https://www.mdpi.com/2073-4409/10/11/3015
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