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Publication : Gene- and Species-Specific Hox mRNA Translation by Ribosome Expansion Segments.

First Author  Leppek K Year  2020
Journal  Mol Cell Volume  80
Issue  6 Pages  980-995.e13
PubMed ID  33202249 Mgi Jnum  J:300170
Mgi Id  MGI:6489727 Doi  10.1016/j.molcel.2020.10.023
Citation  Leppek K, et al. (2020) Gene- and Species-Specific Hox mRNA Translation by Ribosome Expansion Segments. Mol Cell 80(6):980-995.e13
abstractText  Ribosomes have been suggested to directly control gene regulation, but regulatory roles for ribosomal RNA (rRNA) remain largely unexplored. Expansion segments (ESs) consist of multitudes of tentacle-like rRNA structures extending from the core ribosome in eukaryotes. ESs are remarkably variable in sequence and size across eukaryotic evolution with largely unknown functions. In characterizing ribosome binding to a regulatory element within a Homeobox (Hox) 5' UTR, we identify a modular stem-loop within this element that binds to a single ES, ES9S. Engineering chimeric, "humanized" yeast ribosomes for ES9S reveals that an evolutionary change in the sequence of ES9S endows species-specific binding of Hoxa9 mRNA to the ribosome. Genome editing to site-specifically disrupt the Hoxa9-ES9S interaction demonstrates the functional importance for such selective mRNA-rRNA binding in translation control. Together, these studies unravel unexpected gene regulation directly mediated by rRNA and how ribosome evolution drives translation of critical developmental regulators.
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