Nucleolar maturation of the human small subunit processome.

RNA Splicing Factors; RNA, Small Nucleolar; EC 3.6.1.- (DHX38 protein, human); EC 3.6.4.13 (DEAD-box RNA Helicases); Cell Nucleolus/metabolism/ultrastructure; Cryoelectron Microscopy; DEAD-box RNA Helicases/chemistry; Humans; RNA Cleavage; RNA Folding; RNA Splicing Factors/chemistry; RNA Stability; RNA, Small Nucleolar/chemistry

Abstract :

[en] The human small subunit processome mediates early maturation of the small ribosomal subunit by coupling RNA folding to subsequent RNA cleavage and processing steps. We report the high-resolution cryo–electron microscopy structures of maturing human small subunit (SSU) processomes at resolutions of 2.7 to 3.9 angstroms. These structures reveal the molecular mechanisms that enable crucial progressions during SSU processome maturation. RNA folding states within these particles are communicated to and coordinated with key enzymes that drive irreversible steps such as targeted exosome-mediated RNA degradation, protein-guided site-specific endonucleolytic RNA cleavage, and tightly controlled RNA unwinding. These conserved mechanisms highlight the SSU processome’s impressive structural plasticity, which endows this 4.5-megadalton nucleolar assembly with the distinctive ability to mature the small ribosomal subunit from within.

Disciplines :

Biochemistry, biophysics & molecular biology

Author, co-author :

Singh, Sameer ; Laboratory of Protein and Nucleic Acid Chemistry, The Rockefeller University, New York, NY 10065, USA.

Vanden Broeck, Arnaud ; Laboratory of Protein and Nucleic Acid Chemistry, The Rockefeller University, New York, NY 10065, USA.

Miller, Linamarie ; Laboratory of Protein and Nucleic Acid Chemistry, The Rockefeller University, New York, NY 10065, USA. ; Tri-Institutional Training Program in Chemical Biology, The Rockefeller University, New York, NY 10065, USA.

Chaker-Margot, Malik ; Laboratory of Protein and Nucleic Acid Chemistry, The Rockefeller University, New York, NY 10065, USA. ; Tri-Institutional Training Program in Chemical Biology, The Rockefeller University, New York, NY 10065, USA.

Klinge, Sebastian ; Laboratory of Protein and Nucleic Acid Chemistry, The Rockefeller University, New York, NY 10065, USA.

Language :

English

Title :

Nucleolar maturation of the human small subunit processome.

Publication date :

10 September 2021

Journal title :

Science

ISSN :

0036-8075

eISSN :

1095-9203

Publisher :

American Association for the Advancement of Science, Washington, Us dc

Volume :

373

Issue :

6560

Pages :

eabj5338

Peer reviewed :

Peer Reviewed verified by ORBi

Funding number :

DP2 GM123459/GM/NIGMS NIH HHS/United States; R01 GM129325/GM/NIGMS NIH HHS/United States

Available on ORBi :

since 03 October 2024

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