All eubacteria contain SsrA RNA, or tmRNA, which is involved in the rescue of stalled ribosomes. tmRNA acts as both tRNA and mRNA through a process that results in attachment of a C-terminal degradation tag to incomplete polypeptides. A variety of cellular factors are associated with tmRNA function, including ribosomal protein S1. The proposed research seeks to determine the role of S1 in tmRNA-mediated tagging.
The specific aims are (1) to determine which domains of ribosomal protein S1 interact with tmRNA, (2) to determine if S1 is necessary for or accelerates tmRNA-mediated tagging or proteins for degradation, and (3) to dissect tmRNA function at a molecular level with respect to S1 and other factors at distinct points in the tagging process. The domains of S1 involved in tmRNA association will be determined employing truncated S1 proteins. In vitro translation systems employing ribosomes containing truncated S1 proteins will identify which portions of S 1 are necessary for or accelerate tagging. Lastly, modified charged tmRNA or tRNAs will be employed to halt the tagging process at particular points, allowing identification of S1-tmRNA interactions throughout the tagging process. Similar methods may lead to the discovery of new cellular factors involved in tagging. These experiments will generate a molecular and mechanistic view of tagging with respect to S 1 and other factors, and may uncover more general principles of translation regulation.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32GM069138-01
Application #
6691903
Study Section
Special Emphasis Panel (ZRG1-F08 (20))
Program Officer
Wolfe, Paul B
Project Start
2003-08-01
Project End
2005-07-31
Budget Start
2003-08-01
Budget End
2004-07-31
Support Year
1
Fiscal Year
2003
Total Cost
$41,608
Indirect Cost
Name
Massachusetts Institute of Technology
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
001425594
City
Cambridge
State
MA
Country
United States
Zip Code
02139