Abstract:
:A 249-nucleotide coding region instability determinant (CRD) destabilizes c-myc mRNA. Previous experiments identified a CRD-binding protein (CRD-BP) that appears to protect the CRD from endonuclease cleavage. However, it was unclear why a CRD-BP is required to protect a well-translated mRNA whose coding region is covered with ribosomes. We hypothesized that translational pausing in the CRD generates a ribosome-deficient region downstream of the pause site, and this region is exposed to endonuclease attack unless it is shielded by the CRD-BP. Transfection and cell-free translation experiments reported here support this hypothesis. Ribosome pausing occurs within the c-myc CRD in tRNA-depleted reticulocyte translation reactions. The pause sites map to a rare arginine (CGA) codon and to an adjacent threonine (ACA) codon. Changing these codons to more common codons increases translational efficiency in vitro and increases mRNA abundance in transfected cells. These data suggest that c-myc mRNA is rapidly degraded unless it is (i) translated without pausing or (ii) protected by the CRD-BP when pausing occurs. Additional mapping experiments suggest that the CRD is bipartite, with several upstream translation pause sites and a downstream endonuclease cleavage site.
journal_name
Mol Cell Bioljournal_title
Molecular and cellular biologyauthors
Lemm I,Ross Jdoi
10.1128/mcb.22.12.3959-3969.2002subject
Has Abstractpub_date
2002-06-01 00:00:00pages
3959-69issue
12eissn
0270-7306issn
1098-5549journal_volume
22pub_type
杂志文章abstract::The PKC1 gene of Saccharomyces cerevisiae encodes a homolog of mammalian protein kinase C that is required for normal growth and division of yeast cells. We report here the isolation of the yeast MKK1 and MKK2 (for mitogen-activated protein [MAP] kinase-kinase) genes which, when overexpressed, suppress the cell lysis ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.13.5.3076
更新日期:1993-05-01 00:00:00
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pub_type: 杂志文章
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更新日期:1998-12-01 00:00:00
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pub_type: 杂志文章
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pub_type: 杂志文章
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pub_type: 杂志文章
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更新日期:1989-04-01 00:00:00
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pub_type: 杂志文章
doi:10.1128/mcb.16.8.4117
更新日期:1996-08-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.17.12.7283
更新日期:1997-12-01 00:00:00
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pub_type: 杂志文章
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更新日期:1998-01-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.12.3.1292
更新日期:1992-03-01 00:00:00
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pub_type: 杂志文章
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更新日期:2006-12-01 00:00:00
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pub_type: 杂志文章
doi:10.1128/mcb.17.8.4526
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journal_title:Molecular and cellular biology
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
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pub_type: 杂志文章
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pub_type: 杂志文章
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pub_type: 杂志文章
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pub_type: 杂志文章
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更新日期:2005-07-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
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更新日期:1998-03-01 00:00:00