DDX39B promotes translation through regulation of pre-ribosomal RNA levels

ABSTRACT

DDX39B, a DExD RNA helicase, is known to be involved in various cellular processes such as mRNA export, splicing and translation. Previous studies showed that the overexpression of DDX39B promotes the global translation but inhibits the mRNA export in a dominant negative manner. This presents a conundrum as to how DDX39B overexpression would increase the global translation if it inhibits the nuclear export of mRNAs. We resolve this by showing that DDX39B affects the levels of pre-ribosomal RNA by regulating its stability as well as synthesis. Furthermore, DDX39B promotes proliferation and colony forming potential of cells and its levels are significantly elevated in diverse cancer types. Thus, increase in DDX39B enhances global translation and cell proliferation through upregulation of pre-ribosomal RNA. This highlights a possible mechanism by which dysregulation of DDX39B expression could lead to oncogenesis.

KEYWORDS:

• RNA helicase
• pre-ribosomal RNA
• translation
• clonogenic capacity
• cancers

Acknowledgments

We acknowledge DST - FIST and UGC-Special Assistant Programme (SAP) - funded instrumentation facilities of Department of Biotechnology and the Central Instrumentation Facility, Pondicherry University.

Author contributions

S.A. and A.D. designed the study. S.A., B.C., A.M. and P.L.C performed experiments or associated analysis. S.C. performed the bioinformatics analyses. All authors were involved in interpreting the results. S.A., S.C. and A.D. wrote the manuscript. All authors read the manuscript and provided inputs. A.D. conceived, initiated and supervised the study.

Disclosure statement

No potential conflict of interest was reported by the authors.

Supplementary material

Supplemental data for this article can be accessed here.

Additional information

Funding

This work was funded by Innovative Young Biotechnologist Award, Department of Biotechnology, Government of India [BT/03/IYBA/2010 to A.D.]; Council of Scientific and Industrial Research, Government of India (Junior and Senior Research Fellowships to S.A. and B.C.); University Grants Commission, Government of India (BSR-Junior and Senior Research Fellowships to A.M.); Medical Research Council, UK (P.L.C, S.C.).