Architecture and assembly of mammalian H/ACA small nucleolar and telomerase ribonucleoproteins
Open accessAbstract
Mammalian H/ACA small nucleolar RNAs and telomerase RNA share common sequence and secondary structure motifs that form ribonucleoprotein particles (RNPs) with the same four core proteins, NAP57 (also dyskerin or in yeast Cbf5p), GAR1, NHP2, and NOP10. The assembly and molecular interactions of the components of H/ACA RNPs are unknown. Using in vitro transcription/translation in combination with immunoprecipitation of core proteins, UV-crosslinking, and electrophoretic mobility shift assays, we demonstrate the following. NOP10 associates with NAP57 as a prerequisite for NHP2 binding. Although NHP2 on its own binds RNA nonspecifically, this NAP57-NOP10-NHP2 core trimer specifically recognizes H/ACA RNAs. GAR1 associates independently with NAP57 near the pseudouridylase core of mature H/ACA RNPs. In contrast to other RNPs whose assembly is initiated by protein-RNA interactions, the four H/ACA core proteins form a protein-only particle that associates with H/ACA RNAs. Nonetheless, functional H/ACA snoRNPs assembled in cytosolic extracts are stable and do not exchange their RNA components, suggesting that new particle formation requires de novo synthesis.
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Five of the seven identified LTL-associated loci contain genes (TERC, TERT, NAF1, OBFC1, RTEL1) known to be involved in telomere biology.
“Five of the loci contain genes (TERC, TERT, NAF1, OBFC1, RTEL1) that are known to be involved in telomere biology.”
From Identification of seven loci affecting mean telomere length and their association with disease (2013) · cites this paper as [3]
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- Authors
- Wang, C., & Meier, U. T.
- Affiliations
- Albert Einstein College of Medicine (US)
- Corresponding author
- Meier, U Thomas
- Venue
- The EMBO Journal
- Published
- 2004-03-25
- Volume
- 23
- Issue
- 8
- Pages
- 1857-1867
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC394235
- OpenAlex
- W2122834552
- Cited by
- 199
- References
- 67
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 2 · 2023: 12 · 2022: 6 · 2021: 19 · 2020: 4 · 2019: 7 · 2018: 6 · 2017: 4 · 2016: 10 · 2015: 7 · 2014: 7 · 2013: 9 · 2012: 11
- FWCI
- 6.41
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- The EMBO Journal (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Cancer Society
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA modifications and cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
- Keywords
- telomerase RNA, ribonucleoprotein assembly, dyskerin, NOP10, NHP2, GAR1, RNA-protein interactions, RNA recognition, snoRNA processing, telomerase
- MeSH terms
- Animals, Cell Extracts, Humans, Mammals, Mutation, Nuclear Proteins, Protein Binding, RNA, Ultraviolet Rays, Uridine, RNA-Binding Proteins, Ribonucleoproteins, Small Nuclear, Telomerase, RNA, Small Nucleolar, Ribonucleoproteins, Small Nucleolar, Rats
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