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TitleA small nucleolar RNA dictates the structure and function of translating ribosomes in Leishmania.
Journal, issue, pagesNat Commun, Year 2026
Publish dateMar 19, 2026
AuthorsK Shanmugha Rajan / Saurav Aryal / Sharanya Murugeshan / Yinzhou Zhu / Anat Bashan / Mika Olami / Hava Madmoni / Yuko Nobe / Tirza Doniger / Smadar Cohen-Chalamish / Eric Prina / Pascale Pescher / Tom Beneke / Masato Taoka / Christopher L Holley / Ron Unger / Gerald F Späth / Ada Yonath / Shulamit Michaeli /
PubMed AbstractThe most common rRNA modification is 2'-O-methylation. Here, we determine the landscape of 2'-O-methylation in Leishmania, a parasite that cycles between two different hosts, insect and mammalian. We ...The most common rRNA modification is 2'-O-methylation. Here, we determine the landscape of 2'-O-methylation in Leishmania, a parasite that cycles between two different hosts, insect and mammalian. We find two 2'-O-methylated positions that are differentially modified during the parasite's two life stages. The deposition of these modifications is guided by snoRNAs. When we perform cytosine base-editing of the snoRNA responsible for guiding one of the two stage-regulated modifications, Am479, we fail to detect ribosomes lacking this modification, suggesting that it is essential. To better understand the role of the snoRNA and its guided modification, we determine the cryo-EM structures of ribosomes from cells overexpressing the guiding snoRNA and compare them to ribosomes from the parental strain. We do not find structural changes around Am479 or in the small subunit rRNA, but observe a difference in H68 of the large subunit rRNA due to a second base-pairing interaction, suggesting a potential chaperone activity for the snoRNA. Based on these results, translatome and tRNA analysis, we propose a mechanism whereby changes in ribosome structure affect the release of specific tRNAs, which correlate with changes in translation of only a subset of mRNAs.
External linksNat Commun / PubMed:42443220
MethodsEM (single particle)
Resolution1.96 - 2.72 Å
Structure data

18419

8qhu

EMDB-18419, PDB-8qhu:
CRYO-EM STRUCTURE OF LEISHMANIA MAJOR 80S RIBOSOME : LM32Cs1C1 snoRNA overexpression
Method: EM (single particle) / Resolution: 2.72 Å

18437

8qie

EMDB-18437, PDB-8qie:
CRYO-EM STRUCTURE OF LEISHMANIA MAJOR 80S RIBOSOME : LM32Cs1C1 mutant snoRNA overexpression, class 4
Method: EM (single particle) / Resolution: 2.43 Å

50852

9fxo

EMDB-50852, PDB-9fxo:
CRYO-EM STRUCTURE OF LEISHMANIA MAJOR 80S RIBOSOME WITH A/P/E-SITE TRNA AND MRNA : LM32CS1C1 M2 OE MUTANT
Method: EM (single particle) / Resolution: 2.25 Å


EMDB Unreleased entry

EMDB-56552: CLASS-1_APE_CRYO-EM CONSENSUS MAP OF LD32CS1C1 EDITED RIBOSOMES IN COMPLEX WITH MRNA AND TRNA
Method: EM (single particle) / Resolution: 2.26 Å


EMDB Unreleased entry

EMDB-56554: CLASS-2_EP_CRYO-EM CONSENSUS MAP OF LD32CS1C1 EDITED RIBOSOMES IN COMPLEX WITH MRNA AND TRNA
Method: EM (single particle) / Resolution: 2.1 Å


EMDB Unreleased entry

EMDB-56555: CLASS-5_APE_CRYO-EM CONSENSUS MAP OF LD32CS1C1 EDITED RIBOSOMES IN COMPLEX WITH MRNA AND TRNA
Method: EM (single particle) / Resolution: 2.2 Å


EMDB Unreleased entry

EMDB-56556: CLASS-6_APE_CRYO-EM CONSENSUS MAP OF LD32CS1C1 EDITED RIBOSOMES IN COMPLEX WITH MRNA AND TRNA
Method: EM (single particle) / Resolution: 2.18 Å


EMDB Unreleased entry

EMDB-56557: CLASS-7_EP_CRYO-EM CONSENSUS MAP OF LD32CS1C1 EDITED RIBOSOMES IN COMPLEX WITH MRNA AND TRNA
Method: EM (single particle) / Resolution: 2.3 Å


EMDB Unreleased entry

EMDB-57250: Cryo-EM consensus map of lm32cs1c1 m6 overexpression : class 10
Method: EM (single particle) / Resolution: 1.96 Å

Chemicals

ChemComp-MG:
Unknown entry

ChemComp-K:
Unknown entry

ChemComp-NA:
Unknown entry

ChemComp-HOH:
WATER

ChemComp-ZN:
Unknown entry

ChemComp-SPD:
SPERMIDINE

ChemComp-PUT:
1,4-DIAMINOBUTANE

ChemComp-PAR:
PAROMOMYCIN / Antimicrobial, medication*YM

Source
  • leishmania major strain friedlin (eukaryote)
  • Leishmania donovani (eukaryote)
KeywordsRIBOSOME / Leishmania major snoRNA Ribosome / Leishmania major / snoRNA / CRYO-EM / 80S RIBOSOME / TRNA / MRNA

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