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TitleLARP1 binds ribosomes and TOP mRNAs in repressed complexes.
Journal, issue, pagesEMBO J, Vol. 43, Issue 24, Page 6555-6572, Year 2024
Publish dateNov 12, 2024
AuthorsJames A Saba / Zixuan Huang / Kate L Schole / Xianwen Ye / Shrey D Bhatt / Yi Li / Winston Timp / Jingdong Cheng / Rachel Green /
PubMed AbstractTerminal oligopyrimidine motif-containing mRNAs (TOPs) encode all ribosomal proteins in mammals and are regulated to tune ribosome synthesis to cell state. Previous studies have implicated LARP1 in ...Terminal oligopyrimidine motif-containing mRNAs (TOPs) encode all ribosomal proteins in mammals and are regulated to tune ribosome synthesis to cell state. Previous studies have implicated LARP1 in 40S- or 80S-ribosome complexes that are thought to repress and stabilize TOPs. However, a molecular understanding of how LARP1 and TOPs interact with these ribosome complexes is lacking. Here, we show that LARP1 directly binds non-translating ribosomal subunits. Cryo-EM structures reveal a previously uncharacterized domain of LARP1 bound to and occluding the mRNA channel of the 40S subunit. Increased availability of free ribosomal subunits downstream of various stresses promote 60S joining at the same interface to form LARP1-80S complexes. Simultaneously, LARP1 engages the TOP via its previously characterized La/PAM2 and DM15 domains. Contrary to expectations, ribosome binding within these complexes is not required for LARP1-mediated TOP repression or stabilization, two canonical LARP1 functions. Together, this work provides molecular insight into how LARP1 directly binds ribosomal subunits and challenges existing models describing the function of repressed LARP1-40S/80S-TOP complexes.
External linksEMBO J / PubMed:39533057 / PubMed Central
MethodsEM (single particle)
Resolution2.6 - 3.4 Å
Structure data

38548

8xp2

EMDB-38548, PDB-8xp2:
Cryo-EM structure of the human 40S ribosome with LARP1
Method: EM (single particle) / Resolution: 3.2 Å

38549

8xp3

EMDB-38549, PDB-8xp3:
Cryo-EM structure of the human 40S ribosome with LARP1 and LRRC47
Method: EM (single particle) / Resolution: 3.4 Å

EMDB-38550: Cryo-EM structure of the human 40S ribosome with LARP1 (LARP1 pull out)
Method: EM (single particle) / Resolution: 2.6 Å

Chemicals

ChemComp-ZN:
Unknown entry

Source
  • homo sapiens (human)
KeywordsRIBOSOME / 40S ribosome / LARP1 / mTOR / LRRC47

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