Document Detail


Alternatively spliced telomerase reverse transcriptase variants lacking telomerase activity stimulate cell proliferation.
MedLine Citation:
PMID:  22907755     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Eight human and six chicken novel alternatively spliced (AS) variants of telomerase reverse transcriptase (TERT) were identified, including a human variant (Δ4-13) containing an in-frame deletion which removed exons 4 through 13, encoding the catalytic domain of telomerase. This variant was expressed in telomerase-negative normal cells and tissues as well as in transformed telomerase-positive cell lines and cells which employ an alternative method to maintain telomere length. The overexpression of the Δ4-13 variant significantly elevated the proliferation rates of several cell types without enhancing telomerase activity, while decreasing the endogenous expression of this variant by use of small interfering RNA (siRNA) technology reduced cell proliferation. The expression of the Δ4-13 variant stimulated Wnt signaling. In chicken cells, AS TERT variants containing internal deletions or insertions that eliminated or reduced telomerase activity also enhanced cell proliferation. This is the first report that naturally occurring AS TERT variants which lack telomerase activity stimulate cell proliferation.
Authors:
Radmila Hrdlicková; Jirí Nehyba; Henry R Bose
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-08-20
Journal Detail:
Title:  Molecular and cellular biology     Volume:  32     ISSN:  1098-5549     ISO Abbreviation:  Mol. Cell. Biol.     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-10-15     Completed Date:  2013-01-14     Revised Date:  2013-07-12    
Medline Journal Info:
Nlm Unique ID:  8109087     Medline TA:  Mol Cell Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4283-96     Citation Subset:  IM    
Affiliation:
Section of Molecular Genetics and Microbiology, School of Biological Science, and Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, Texas, USA.
Data Bank Information
Bank Name/Acc. No.:
GENBANK/DQ681296;  DQ681297;  DQ681298;  DQ681311;  DQ681312;  JF896279;  JF896280;  JF896281;  JF896282;  JF896283;  JF896284;  JF896285;  JF896286
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MeSH Terms
Descriptor/Qualifier:
Alternative Splicing*
Animals
Cell Line, Tumor
Cell Proliferation*
Chickens
DNA-Binding Proteins / genetics,  metabolism
Genetic Variation
HeLa Cells
Humans
Molecular Sequence Data
Mutation
RNA Interference
RNA, Messenger / genetics
RNA, Small Interfering
Telomerase / genetics*,  metabolism*
Telomere / metabolism
Wnt Signaling Pathway*
Grant Support
ID/Acronym/Agency:
CA098151/CA/NCI NIH HHS; CA33192/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/DNA-Binding Proteins; 0/RNA, Messenger; 0/RNA, Small Interfering; EC 2.7.7.49/TERT protein, human; EC 2.7.7.49/Telomerase
Comments/Corrections

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