The multifunctional RNA-binding protein hnRNP A1 is required for processing of miR-18a
Abstract
hnRNP A1 is an RNA-binding protein involved in various aspects of RNA processing. Use of an in vivo cross-linking and immunoprecipitation protocol to find hnRNP A1 RNA targets resulted in the identification of a microRNA (miRNA) precursor, pre-miR-18a. This microRNA is expressed as part of a cluster of intronic RNAs, including miR-17, miR-18a, miR-19a, miR-20a, miR-19b-1 and miR-92, and potentially acts as an oncogene. Here we show that hnRNP A1 binds specifically to the primary RNA sequence pri-miR-18a before Drosha processing. HeLa cells depleted of hnRNP A1 have reduced in vitro processing activity with pri-miR-18a and also show reduced abundances of endogenous pre-miR-18a. Furthermore, we show that hnRNP A1 is required for miR-18a-mediated repression of a target reporter in vivo. These results underscore a previously uncharacterized role for general RNA-binding proteins as auxiliary factors that facilitate the processing of specific miRNAs.
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RBPs modulate miRNA biogenesis, stability, and localization through alternative processing and/or maturation.
“or RBPs modulate miRNA biogenesis, stability, and localization through alternative processing and/or maturation (Guil and Cáceres 2007; Michlewski and Cáceres 2010, 2019; Choudhury et al. 2013; Treiber et al. 2017; Nussbacher and Yeo 2018; Yeom et al. 2018).”
From ESRP2–microRNA-122 axis promotes the postnatal onset of liver polyploidization and maturation (2025) · cites this paper as Guil and Cáceres 2007
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- Authors
- Guil, S., & Cáceres, J. F.
- Affiliations
- Western General Hospital (GB)
- Corresponding author
- Cáceres, Javier F
- ORCID
- Cáceres, Javier F
- Venue
- Nature Structural & Molecular Biology
- Published
- 2007-06-10
- Volume
- 14
- Issue
- 7
- Pages
- 591-596
- ISSN
- 1545-9985 (ISSN-L)
- 1545-9993
- OpenAlex
- W2079248832
- Cited by
- 567
- References
- 42
- Citations by year
- 2026: 7 · 2025: 11 · 2024: 10 · 2023: 12 · 2022: 16 · 2021: 36 · 2020: 27 · 2019: 20 · 2018: 26 · 2017: 35 · 2016: 18 · 2015: 40 · 2014: 40 · 2013: 44 · 2012: 41
- FWCI
- 15.27
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Structural & Molecular Biology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Plant Molecular Biology Research
- Keywords
- hnRNP A1, miR-18a, microRNA processing, RNA-binding proteins, Drosha, microRNA precursors, miR-17-92 cluster, RNA target identification, gene repression, oncogenic microRNA
- MeSH terms
- Heterogeneous Nuclear Ribonucleoprotein A1, Gene Expression Regulation, HeLa Cells, Humans, RNA Precursors, RNA-Binding Proteins, Heterogeneous-Nuclear Ribonucleoprotein Group A-B, MicroRNAs, Ribonuclease III
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