Journal article
Multiple myeloma–associated chromosomal translocation activates orphan snoRNA ACA11 to suppress oxidative stress
The Journal of clinical investigation, Vol.122(8), pp.2793-2806
08/01/2012
DOI: 10.1172/JCI63051
PMCID: PMC3408744
PMID: 22751105
Abstract
The histone methyltransferase WHSC1 (also known as MMSET) is overexpressed in multiple myeloma (MM) as a result of the t(4;14) chromosomal translocation and in a broad variety of other cancers by unclear mechanisms. Overexpression of WHSC1 did not transform wild-type or tumor-prone primary hematopoietic cells. We found that ACA11, an orphan box H/ACA class small nucleolar RNA (snoRNA) encoded within an intron of
WHSC1
, was highly expressed in t(4;14)-positive MM and other cancers. ACA11 localized to nucleoli and bound what we believe to be a novel small nuclear ribonucleoprotein (snRNP) complex composed of several proteins involved in postsplicing intron complexes. RNA targets of this uncharacterized snRNP included snoRNA intermediates hosted within ribosomal protein (RP) genes, and an RP gene signature was strongly associated with t(4;14) in patients with MM. Expression of ACA11 was sufficient to downregulate RP genes and other snoRNAs implicated in the control of oxidative stress. ACA11 suppressed oxidative stress, afforded resistance to chemotherapy, and increased the proliferation of MM cells, demonstrating that ACA11 is a critical target of the t(4;14) translocation in MM and suggesting an oncogenic role in other cancers as well.
Details
- Title: Subtitle
- Multiple myeloma–associated chromosomal translocation activates orphan snoRNA ACA11 to suppress oxidative stress
- Creators
- Liang Chu - Division of Oncology andMichael H Tomasson - Division of Oncology andMack Y Su - Division of Oncology andLeonard B Maggi - Division of Oncology andLan Lu - Division of Oncology andChelsea Mullins - Division of Oncology andSeth Crosby - Division of Oncology andGaofeng Huang - Division of Oncology andWee Joo Chng - Division of Oncology andRavi Vij - Division of Oncology and
- Resource Type
- Journal article
- Publication Details
- The Journal of clinical investigation, Vol.122(8), pp.2793-2806
- Publisher
- American Society for Clinical Investigation
- DOI
- 10.1172/JCI63051
- PMID
- 22751105
- PMCID
- PMC3408744
- ISSN
- 0021-9738
- eISSN
- 1558-8238
- Language
- English
- Date published
- 08/01/2012
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984094573202771
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