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Exploring Sequence Space to Identify Binding Sites for Regulatory RNA-Binding Proteins
Published on: August 9, 2019
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Cytoplasmic poly(A) binding protein-1 binds to genomically encoded sequences within mammalian mRNAs
Hemant K Kini1, Ian M Silverman2, Xinjun Ji1
1Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, 19104, USA.
RNA (New York, N.Y.)
|November 11, 2015
Summary
Poly(A)-binding protein (PABPC1) binds to more mRNA sites than previously known, including within coding regions and 5' UTRs. These novel interactions regulate gene expression through translation control.
Area of Science:
- Molecular Biology
- Gene Regulation
- RNA Biology
Background:
- Cytoplasmic poly(A)-binding protein 1 (PABPC1) is crucial for mRNA regulation.
- PABPC1 primarily binds to the 3' poly(A) tail, influencing translation and mRNA stability.
Purpose of the Study:
- To identify novel PABPC1 binding sites across the transcriptome.
- To investigate the regulatory roles of PABPC1 beyond its canonical poly(A) tail interactions.
Main Methods:
- Transcriptome-wide crosslinking and immunoprecipitation sequencing (CLIP-seq) in mice.
- Analysis of PABPC1 binding sites within mRNA sequences.
- Functional assays for 5' UTR binding interactions.
Main Results:
- PABPC1 binds to the canonical polyadenylation signal in thousands of mouse mRNAs.
- PABPC1 also binds to translation initiation/termination sites and A-rich sequences in 5' UTRs.
- 5' UTR binding mediates auto- and trans-regulatory translational control.
Conclusions:
- PABPC1 possesses a broader mRNA binding repertoire than previously understood.
- These novel interactions significantly expand PABPC1's role in post-transcriptional gene regulation.
- PABPC1 can coordinate cellular functions through diverse mRNA binding activities.
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