DDX49 is an RNA helicase that affects translation by regulating mRNA export and the levels of pre-ribosomal RNA

Sharad Awasthi; Mamta Verma; Arun Mahesh; Mohd Imran K. Khan; Gayathri Govindaraju; Arumugam Rajavelu; Pavithra L Chavali; Sreenivas Chavali; Arunkumar Dhayalan

doi:10.1093/nar/gky231

DDX49 is an RNA helicase that affects translation by regulating mRNA export and the levels of pre-ribosomal RNA

Sharad Awasthi, Mamta Verma, Arun Mahesh, Mohd Imran K. Khan, Gayathri Govindaraju, Arumugam Rajavelu, Pavithra L Chavali, Sreenivas Chavali^*, Arunkumar Dhayalan^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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Abstract

Among the proteins predicted to be a part of the DExD box RNA helicase family, the functions of DDX49 are unknown. Here, we characterize the enzymatic activities and functions of DDX49 by comparing its properties with the well-studied RNA helicase, DDX39B. We find that DDX49 exhibits a robust ATPase and RNA helicase activity, significantly higher than that of DDX39B. DDX49 is required for the efficient export of poly (A) + RNA from nucleus in a splicing-independent manner. Furthermore, DDX49 is a resident protein of nucleolus and regulates the steady state levels of pre-ribosomal RNA by regulating its transcription and stability. These dual functions of regulating mRNA export and pre-ribosomal RNA levels enable DDX49 to modulate global translation. Phenotypically, DDX49 promotes proliferation and colony forming potential of cells. Strikingly, DDX49 is significantly elevated in diverse cancer types suggesting that the increased abundance of DDX49 has a role in oncogenic transformation of cells. Taken together, this study shows the physiological role of DDX49 in regulating distinct steps of mRNA and pre-ribosomal RNA metabolism and hence translation and potential pathological role of its dysregulation, especially in cancers.

Original language	English
Pages (from-to)	6304-6317
Journal	Nucleic Acids Research
Volume	46
Issue number	12
Early online date	30 Mar 2018
DOIs	https://doi.org/10.1093/nar/gky231
Publication status	Published - 06 Jul 2018
Externally published	Yes

ASJC Scopus subject areas

Genetics

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10.1093/nar/gky231Licence: CC BY

DDX49 is an RNA helicase that affects translation by regulating mRNA export and the levels of pre-ribosomal RNA
Copyright 2018 The Authors. This is an open access article published under a Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited.
Final published version, 2.98 MBLicence: CC BY

Cite this

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title = "DDX49 is an RNA helicase that affects translation by regulating mRNA export and the levels of pre-ribosomal RNA",

abstract = "Among the proteins predicted to be a part of the DExD box RNA helicase family, the functions of DDX49 are unknown. Here, we characterize the enzymatic activities and functions of DDX49 by comparing its properties with the well-studied RNA helicase, DDX39B. We find that DDX49 exhibits a robust ATPase and RNA helicase activity, significantly higher than that of DDX39B. DDX49 is required for the efficient export of poly (A) + RNA from nucleus in a splicing-independent manner. Furthermore, DDX49 is a resident protein of nucleolus and regulates the steady state levels of pre-ribosomal RNA by regulating its transcription and stability. These dual functions of regulating mRNA export and pre-ribosomal RNA levels enable DDX49 to modulate global translation. Phenotypically, DDX49 promotes proliferation and colony forming potential of cells. Strikingly, DDX49 is significantly elevated in diverse cancer types suggesting that the increased abundance of DDX49 has a role in oncogenic transformation of cells. Taken together, this study shows the physiological role of DDX49 in regulating distinct steps of mRNA and pre-ribosomal RNA metabolism and hence translation and potential pathological role of its dysregulation, especially in cancers.",

author = "Sharad Awasthi and Mamta Verma and Arun Mahesh and Khan, {Mohd Imran K.} and Gayathri Govindaraju and Arumugam Rajavelu and Chavali, {Pavithra L} and Sreenivas Chavali and Arunkumar Dhayalan",

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doi = "10.1093/nar/gky231",

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AU - Awasthi, Sharad

AU - Verma, Mamta

AU - Mahesh, Arun

AU - Khan, Mohd Imran K.

AU - Govindaraju, Gayathri

AU - Rajavelu, Arumugam

AU - Chavali, Pavithra L

AU - Chavali, Sreenivas

AU - Dhayalan, Arunkumar

PY - 2018/7/6

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N2 - Among the proteins predicted to be a part of the DExD box RNA helicase family, the functions of DDX49 are unknown. Here, we characterize the enzymatic activities and functions of DDX49 by comparing its properties with the well-studied RNA helicase, DDX39B. We find that DDX49 exhibits a robust ATPase and RNA helicase activity, significantly higher than that of DDX39B. DDX49 is required for the efficient export of poly (A) + RNA from nucleus in a splicing-independent manner. Furthermore, DDX49 is a resident protein of nucleolus and regulates the steady state levels of pre-ribosomal RNA by regulating its transcription and stability. These dual functions of regulating mRNA export and pre-ribosomal RNA levels enable DDX49 to modulate global translation. Phenotypically, DDX49 promotes proliferation and colony forming potential of cells. Strikingly, DDX49 is significantly elevated in diverse cancer types suggesting that the increased abundance of DDX49 has a role in oncogenic transformation of cells. Taken together, this study shows the physiological role of DDX49 in regulating distinct steps of mRNA and pre-ribosomal RNA metabolism and hence translation and potential pathological role of its dysregulation, especially in cancers.

AB - Among the proteins predicted to be a part of the DExD box RNA helicase family, the functions of DDX49 are unknown. Here, we characterize the enzymatic activities and functions of DDX49 by comparing its properties with the well-studied RNA helicase, DDX39B. We find that DDX49 exhibits a robust ATPase and RNA helicase activity, significantly higher than that of DDX39B. DDX49 is required for the efficient export of poly (A) + RNA from nucleus in a splicing-independent manner. Furthermore, DDX49 is a resident protein of nucleolus and regulates the steady state levels of pre-ribosomal RNA by regulating its transcription and stability. These dual functions of regulating mRNA export and pre-ribosomal RNA levels enable DDX49 to modulate global translation. Phenotypically, DDX49 promotes proliferation and colony forming potential of cells. Strikingly, DDX49 is significantly elevated in diverse cancer types suggesting that the increased abundance of DDX49 has a role in oncogenic transformation of cells. Taken together, this study shows the physiological role of DDX49 in regulating distinct steps of mRNA and pre-ribosomal RNA metabolism and hence translation and potential pathological role of its dysregulation, especially in cancers.

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DO - 10.1093/nar/gky231

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DDX49 is an RNA helicase that affects translation by regulating mRNA export and the levels of pre-ribosomal RNA

Abstract

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