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Updated: Apr 23, 2026

Isolation of Translating Ribosomes Containing Peptidyl-tRNAs for Functional and Structural Analyses
Published on: February 25, 2011
The race to decipher the top secrets of TOP mRNAs
1Department of Biochemistry and Molecular Biology, Institute for Medical Research - Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel.
Abstract:
Cells encountering hostile growth conditions, like those residing in the middle of a newly developing solid tumor, conserve resources and energy by downregulating protein synthesis. One mechanism in this response is the translational repression of multiple mRNAs that encode components of the translational apparatus. This coordinated translational control is carried through a common cis-regulatory element, the 5' Terminal OligoPyrimidine motif (5'TOP), after which these mRNAs are referred to as TOP mRNAs. Subsequent to the initial structural and functional characterization of members of this family, the research of TOP mRNAs has progressed in three major directions: a) delineating the landscape of the family; b) establishing the pathways that transduce stress cues into selective translational repression; and c) attempting to decipher the most proximal trans-acting factor(s) and defining its mode of action--a repressor or activator. The present chapter critically reviews the development in these three avenues of research with a special emphasis on the two "top secrets" of the TOP mRNA family: the scope of its members and the identity of the proximal cellular regulator(s). This article is part of a Special Issue entitled: Translation and Cancer.
Insights
Cells under stress, such as in tumors, reduce protein synthesis by repressing 5' Terminal OligoPyrimidine (5'TOP) mRNAs. Research focuses on identifying TOP mRNA family members and the regulators controlling this translational repression.
Area of Science:
- Molecular Biology
- Cellular Stress Response
- Cancer Biology
Background:
- Cells in harsh environments, like solid tumors, conserve energy by limiting protein synthesis.
- This involves downregulating the translation of specific messenger RNAs (mRNAs).
- A key mechanism utilizes the 5' Terminal OligoPyrimidine (5'TOP) motif present in these mRNAs, termed TOP mRNAs.
Purpose of the Study:
- To review the current understanding of TOP mRNAs.
- To highlight research progress in identifying TOP mRNA family members.
- To discuss the pathways and factors regulating TOP mRNA translational repression during cellular stress.
Main Methods:
- Literature review and critical analysis of existing research on TOP mRNAs.
- Focus on studies investigating the scope of TOP mRNA family members.
- Examination of research defining stress-induced translational control pathways and regulatory factors.
Main Results:
- The research landscape of TOP mRNAs has expanded significantly.
- Progress has been made in identifying the full range of TOP mRNA targets.
- Understanding of the signaling pathways and proximal regulators governing TOP mRNA repression is advancing.
Conclusions:
- TOP mRNAs represent a crucial mechanism for cellular resource conservation under stress.
- Further research is needed to fully elucidate the complete set of TOP mRNAs and their precise regulatory mechanisms.
- Understanding TOP mRNA regulation is vital for insights into cancer biology and therapeutic strategies.
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