The 3' to 5' exoribonuclease DIS3: from structure and mechanisms to biological functions and role in human disease

Robinson, Sophie R, Oliver, Antony W, Chevassut, Timothy J and Newbury, Sarah F (2015) The 3' to 5' exoribonuclease DIS3: from structure and mechanisms to biological functions and role in human disease. Biomolecules, 5 (3). pp. 1515-1539. ISSN 2218-273X

[img]
Preview
PDF - Published Version
Available under License Creative Commons Attribution.

Download (3MB) | Preview

Abstract

DIS3 is a conserved exoribonuclease and catalytic subunit of the exosome, a protein complex involved in the 3’ to 5’ degradation and processing of both nuclear and cytoplasmic RNA species. Recently, aberrant expression of DIS3 has been found to be implicated in a range of different cancers. Perhaps most striking is the finding that DIS3 is recurrently mutated in 11% of multiple myeloma patients. Much work has been done to elucidate the structural and biochemical characteristics of DIS3, including the mechanistic details of its role as an effector of RNA decay pathways. Nevertheless, we do not understand how DIS3 mutations can lead to cancer. There are a number of studies that pertain to the function of DIS3 at the organismal level. Mutant phenotypes in S.pombe, S.cerevisae and Drosophila suggest DIS3 homologues have a common role in cell-cycle progression and microtubule assembly. DIS3 has also recently been implicated in antibody diversification of mouse B-cells. This article aims to review current knowledge of the structure, mechanisms and functions of DIS3 as well as highlighting the genetic patterns observed within myeloma patients, in order to yield insight into the putative role of DIS3 mutations in oncogenesis.

Item Type: Article
Keywords: RNA stability, ribonucleases, microRNAs, Dis3, myeloma
Schools and Departments: Brighton and Sussex Medical School > Brighton and Sussex Medical School
School of Life Sciences > Sussex Centre for Genome Damage and Stability
Brighton and Sussex Medical School > Clinical and Experimental Medicine
Subjects: R Medicine > RB Pathology > RB037 Clinical pathology. Laboratory technique
R Medicine > RD Surgery > RD0651 Neoplasms. Tumors. Oncology
Depositing User: Sarah Newbury
Date Deposited: 14 Sep 2015 14:31
Last Modified: 21 Sep 2017 18:38
URI: http://sro.sussex.ac.uk/id/eprint/56747

View download statistics for this item

📧 Request an update
Project NameSussex Project NumberFunderFunder Ref
Ph.D studentshipWC003-14BSMSWC003-14
Epigenetic regulation of gene expression by the exoribonuclease pacmanG0056BBSRC-BIOTECHNOLOGY & BIOLOGICAL SCIENCES RESEARCH COUNCILBB/I021345/1