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TitleGene- and Species-Specific Hox mRNA Translation by Ribosome Expansion Segments.
Journal, issue, pagesMol Cell, Vol. 80, Issue 6, Page 980-995.e13, Year 2020
Publish dateDec 17, 2020
AuthorsKathrin Leppek / Kotaro Fujii / Nick Quade / Teodorus Theo Susanto / Daniel Boehringer / Tea Lenarčič / Shifeng Xue / Naomi R Genuth / Nenad Ban / Maria Barna /
PubMed AbstractRibosomes 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- ...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.
External linksMol Cell / PubMed:33202249 / PubMed Central
MethodsEM (single particle)
Resolution3.1 - 4.4 Å
Structure data

EMDB-11562:
Mouse Hoxa9 IRES like element bound to the human 80S ribosome
Method: EM (single particle) / Resolution: 4.4 Å

EMDB-11563:
Mouse Hoxa9 IRES-like element bound to the human 40S ribosomal subunit head - IRES binding site
Method: EM (single particle) / Resolution: 3.9 Å

EMDB-11564:
Mouse Hoxa9 IRES-like element bound to the human 40S ribosomal subunit - 40S head
Method: EM (single particle) / Resolution: 3.3 Å

EMDB-11565:
Mouse Hoxa9 IRES-like element bound to the human 40S ribosomal subunit - 40S body
Method: EM (single particle) / Resolution: 3.3 Å

EMDB-11566:
Hoxa9 IRES P4 stem-loop bound to the 40S ribosomal subunit - 40S head
Method: EM (single particle) / Resolution: 4.1 Å

EMDB-11567:
Hoxa9 IRES P4 stem-loop bound to the 40S ribosomal subunit - 40S body
Method: EM (single particle) / Resolution: 3.1 Å

EMDB-11568:
human 40S ribosomal subunit (control)
Method: EM (single particle) / Resolution: 3.2 Å

Source
  • Homo sapiens (human)

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