Identification of novel proteins and mRNAs differentially bound to the Leishmania Poly(A) Binding Proteins reveals a direct association between PABP1, the RNA-binding protein RBP23 and mRNAs encoding ribosomal proteins.

Poly(A) Binding Proteins (PABPs) are major eukaryotic RNA-binding proteins (RBPs) with multiple roles associated with mRNA stability and translation and characterized mainly from multicellular organisms and yeasts. A variable number of PABP homologues are seen in different organisms however the biol...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Ludmila A Assis, Moezio V C Santos Filho, Joao R da Cruz Silva, Maria J R Bezerra, Irassandra R P U C de Aquino, Kleison C Merlo, Fabiola B Holetz, Christian M Probst, Antonio M Rezende, Barbara Papadopoulou, Tamara D C da Costa Lima, Osvaldo P de Melo Neto
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270
Acceso en línea:	https://doaj.org/article/7582158e93974ec7b0804d1be9beaee2
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:7582158e93974ec7b0804d1be9beaee2
record_format	dspace
spelling	oai:doaj.org-article:7582158e93974ec7b0804d1be9beaee22021-12-02T20:23:27ZIdentification of novel proteins and mRNAs differentially bound to the Leishmania Poly(A) Binding Proteins reveals a direct association between PABP1, the RNA-binding protein RBP23 and mRNAs encoding ribosomal proteins.1935-27271935-273510.1371/journal.pntd.0009899https://doaj.org/article/7582158e93974ec7b0804d1be9beaee22021-10-01T00:00:00Zhttps://doi.org/10.1371/journal.pntd.0009899https://doaj.org/toc/1935-2727https://doaj.org/toc/1935-2735Poly(A) Binding Proteins (PABPs) are major eukaryotic RNA-binding proteins (RBPs) with multiple roles associated with mRNA stability and translation and characterized mainly from multicellular organisms and yeasts. A variable number of PABP homologues are seen in different organisms however the biological reasons for multiple PABPs are generally not well understood. In the unicellular Leishmania, dependent on post-transcriptional mechanisms for the control of its gene expression, three distinct PABPs are found, with yet undefined functional distinctions. Here, using RNA-immunoprecipitation sequencing analysis we show that the Leishmania PABP1 preferentially associates with mRNAs encoding ribosomal proteins, while PABP2 and PABP3 bind to an overlapping set of mRNAs distinct to those enriched in PABP1. Immunoprecipitation studies combined to mass-spectrometry analysis identified RBPs differentially associated with PABP1 or PABP2, including RBP23 and DRBD2, respectively, that were investigated further. Both RBP23 and DRBD2 bind directly to the three PABPs in vitro, but reciprocal experiments confirmed preferential co-immunoprecipitation of PABP1, as well as the EIF4E4/EIF4G3 based translation initiation complex, with RBP23. Other RBP23 binding partners also imply a direct role in translation. DRBD2, in contrast, co-immunoprecipitated with PABP2, PABP3 and with RBPs unrelated to translation. Over 90% of the RBP23-bound mRNAs code for ribosomal proteins, mainly absent from the transcripts co-precipitated with DRBD2. These experiments suggest a novel and specific route for translation of the ribosomal protein mRNAs, mediated by RBP23, PABP1 and the associated EIF4E4/EIF4G3 complex. They also highlight the unique roles that different PABP homologues may have in eukaryotic cells associated with mRNA translation.Ludmila A AssisMoezio V C Santos FilhoJoao R da Cruz SilvaMaria J R BezerraIrassandra R P U C de AquinoKleison C MerloFabiola B HoletzChristian M ProbstAntonio M RezendeBarbara PapadopoulouTamara D C da Costa LimaOsvaldo P de Melo NetoPublic Library of Science (PLoS)articleArctic medicine. Tropical medicineRC955-962Public aspects of medicineRA1-1270ENPLoS Neglected Tropical Diseases, Vol 15, Iss 10, p e0009899 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270
spellingShingle	Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Ludmila A Assis Moezio V C Santos Filho Joao R da Cruz Silva Maria J R Bezerra Irassandra R P U C de Aquino Kleison C Merlo Fabiola B Holetz Christian M Probst Antonio M Rezende Barbara Papadopoulou Tamara D C da Costa Lima Osvaldo P de Melo Neto Identification of novel proteins and mRNAs differentially bound to the Leishmania Poly(A) Binding Proteins reveals a direct association between PABP1, the RNA-binding protein RBP23 and mRNAs encoding ribosomal proteins.
description	Poly(A) Binding Proteins (PABPs) are major eukaryotic RNA-binding proteins (RBPs) with multiple roles associated with mRNA stability and translation and characterized mainly from multicellular organisms and yeasts. A variable number of PABP homologues are seen in different organisms however the biological reasons for multiple PABPs are generally not well understood. In the unicellular Leishmania, dependent on post-transcriptional mechanisms for the control of its gene expression, three distinct PABPs are found, with yet undefined functional distinctions. Here, using RNA-immunoprecipitation sequencing analysis we show that the Leishmania PABP1 preferentially associates with mRNAs encoding ribosomal proteins, while PABP2 and PABP3 bind to an overlapping set of mRNAs distinct to those enriched in PABP1. Immunoprecipitation studies combined to mass-spectrometry analysis identified RBPs differentially associated with PABP1 or PABP2, including RBP23 and DRBD2, respectively, that were investigated further. Both RBP23 and DRBD2 bind directly to the three PABPs in vitro, but reciprocal experiments confirmed preferential co-immunoprecipitation of PABP1, as well as the EIF4E4/EIF4G3 based translation initiation complex, with RBP23. Other RBP23 binding partners also imply a direct role in translation. DRBD2, in contrast, co-immunoprecipitated with PABP2, PABP3 and with RBPs unrelated to translation. Over 90% of the RBP23-bound mRNAs code for ribosomal proteins, mainly absent from the transcripts co-precipitated with DRBD2. These experiments suggest a novel and specific route for translation of the ribosomal protein mRNAs, mediated by RBP23, PABP1 and the associated EIF4E4/EIF4G3 complex. They also highlight the unique roles that different PABP homologues may have in eukaryotic cells associated with mRNA translation.
format	article
author	Ludmila A Assis Moezio V C Santos Filho Joao R da Cruz Silva Maria J R Bezerra Irassandra R P U C de Aquino Kleison C Merlo Fabiola B Holetz Christian M Probst Antonio M Rezende Barbara Papadopoulou Tamara D C da Costa Lima Osvaldo P de Melo Neto
author_facet	Ludmila A Assis Moezio V C Santos Filho Joao R da Cruz Silva Maria J R Bezerra Irassandra R P U C de Aquino Kleison C Merlo Fabiola B Holetz Christian M Probst Antonio M Rezende Barbara Papadopoulou Tamara D C da Costa Lima Osvaldo P de Melo Neto
author_sort	Ludmila A Assis
title	Identification of novel proteins and mRNAs differentially bound to the Leishmania Poly(A) Binding Proteins reveals a direct association between PABP1, the RNA-binding protein RBP23 and mRNAs encoding ribosomal proteins.
title_short	Identification of novel proteins and mRNAs differentially bound to the Leishmania Poly(A) Binding Proteins reveals a direct association between PABP1, the RNA-binding protein RBP23 and mRNAs encoding ribosomal proteins.
title_full	Identification of novel proteins and mRNAs differentially bound to the Leishmania Poly(A) Binding Proteins reveals a direct association between PABP1, the RNA-binding protein RBP23 and mRNAs encoding ribosomal proteins.
title_fullStr	Identification of novel proteins and mRNAs differentially bound to the Leishmania Poly(A) Binding Proteins reveals a direct association between PABP1, the RNA-binding protein RBP23 and mRNAs encoding ribosomal proteins.
title_full_unstemmed	Identification of novel proteins and mRNAs differentially bound to the Leishmania Poly(A) Binding Proteins reveals a direct association between PABP1, the RNA-binding protein RBP23 and mRNAs encoding ribosomal proteins.
title_sort	identification of novel proteins and mrnas differentially bound to the leishmania poly(a) binding proteins reveals a direct association between pabp1, the rna-binding protein rbp23 and mrnas encoding ribosomal proteins.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/7582158e93974ec7b0804d1be9beaee2
work_keys_str_mv	AT ludmilaaassis identificationofnovelproteinsandmrnasdifferentiallyboundtotheleishmaniapolyabindingproteinsrevealsadirectassociationbetweenpabp1thernabindingproteinrbp23andmrnasencodingribosomalproteins AT moeziovcsantosfilho identificationofnovelproteinsandmrnasdifferentiallyboundtotheleishmaniapolyabindingproteinsrevealsadirectassociationbetweenpabp1thernabindingproteinrbp23andmrnasencodingribosomalproteins AT joaordacruzsilva identificationofnovelproteinsandmrnasdifferentiallyboundtotheleishmaniapolyabindingproteinsrevealsadirectassociationbetweenpabp1thernabindingproteinrbp23andmrnasencodingribosomalproteins AT mariajrbezerra identificationofnovelproteinsandmrnasdifferentiallyboundtotheleishmaniapolyabindingproteinsrevealsadirectassociationbetweenpabp1thernabindingproteinrbp23andmrnasencodingribosomalproteins AT irassandrarpucdeaquino identificationofnovelproteinsandmrnasdifferentiallyboundtotheleishmaniapolyabindingproteinsrevealsadirectassociationbetweenpabp1thernabindingproteinrbp23andmrnasencodingribosomalproteins AT kleisoncmerlo identificationofnovelproteinsandmrnasdifferentiallyboundtotheleishmaniapolyabindingproteinsrevealsadirectassociationbetweenpabp1thernabindingproteinrbp23andmrnasencodingribosomalproteins AT fabiolabholetz identificationofnovelproteinsandmrnasdifferentiallyboundtotheleishmaniapolyabindingproteinsrevealsadirectassociationbetweenpabp1thernabindingproteinrbp23andmrnasencodingribosomalproteins AT christianmprobst identificationofnovelproteinsandmrnasdifferentiallyboundtotheleishmaniapolyabindingproteinsrevealsadirectassociationbetweenpabp1thernabindingproteinrbp23andmrnasencodingribosomalproteins AT antoniomrezende identificationofnovelproteinsandmrnasdifferentiallyboundtotheleishmaniapolyabindingproteinsrevealsadirectassociationbetweenpabp1thernabindingproteinrbp23andmrnasencodingribosomalproteins AT barbarapapadopoulou identificationofnovelproteinsandmrnasdifferentiallyboundtotheleishmaniapolyabindingproteinsrevealsadirectassociationbetweenpabp1thernabindingproteinrbp23andmrnasencodingribosomalproteins AT tamaradcdacostalima identificationofnovelproteinsandmrnasdifferentiallyboundtotheleishmaniapolyabindingproteinsrevealsadirectassociationbetweenpabp1thernabindingproteinrbp23andmrnasencodingribosomalproteins AT osvaldopdemeloneto identificationofnovelproteinsandmrnasdifferentiallyboundtotheleishmaniapolyabindingproteinsrevealsadirectassociationbetweenpabp1thernabindingproteinrbp23andmrnasencodingribosomalproteins
_version_	1718374114158182400

Identification of novel proteins and mRNAs differentially bound to the Leishmania Poly(A) Binding Proteins reveals a direct association between PABP1, the RNA-binding protein RBP23 and mRNAs encoding ribosomal proteins.

Ejemplares similares