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NEAT1 scaffolds RNA-binding proteins and the Microprocessor to globally enhance pri-miRNA processing.

Li Jiang, Changwei Shao, Qi-Jia Wu, Geng Chen, Jie Zhou, Bo Yang, Hairi Li, Lan-Tao Gou, Yi Zhang, Yangming Wang, Gene W Yeo, Yu Zhou, Xiang-Dong Fu
Nature structural & molecular biology · 2017 · Vol. 24 (10) · pp. 816-824
PubMed DOI PMC Full Text

Abstract

MicroRNA (miRNA) biogenesis is known to be modulated by a variety of RNA-binding proteins (RBPs), but in most cases, individual RBPs appear to influence the processing of a small subset of target miRNAs. Here, we report that the RNA-binding NONO-PSF heterodimer binds a large number of expressed pri-miRNAs in HeLa cells to globally enhance pri-miRNA processing by the Drosha-DGCR8 Microprocessor. NONO and PSF are key components of paraspeckles organized by the long noncoding RNA (lncRNA) NEAT1. We further demonstrate that NEAT1 also has a profound effect on global pri-miRNA processing. Mechanistic dissection reveals that NEAT1 broadly interacts with the NONO-PSF heterodimer as well as many other RBPs and that multiple RNA segments in NEAT1, including a 'pseudo pri-miRNA' near its 3' end, help attract the Microprocessor. These findings suggest a 'bird nest' model in which an lncRNA orchestrates efficient processing of potentially an entire class of small noncoding RNAs in the nucleus.

Publication Types

["Journal Article"]

Keywords

[]

MeSH Terms

["DNA-Binding Proteins", "HeLa Cells", "Humans", "MicroRNAs", "Nuclear Matrix-Associated Proteins", "Octamer Transcription Factors", "PTB-Associated Splicing Factor", "Protein Binding", "RNA Processing, Post-Transcriptional", "RNA, Long Noncoding", "RNA-Binding Proteins", "Ribonuclease III"]

Funding

R01 HG004659 NHGRI NIH HHS (United States)
R01 GM052872 NIGMS NIH HHS (United States)
R01 GM049369 NIGMS NIH HHS (United States)

Linked Datasets (1)

GSE90650 GSE via ncbi_elink
GEO

The LncRNA NEAT1 Nests RNA Binding Proteins and the Microprocessor to Globally Enhance Pri-miRNA Processing

Homo sapiens
32 data files
FileTypeSize
NONO-1.fastq.gz OTHER 933.8 MB
NONO-1.fastq.gz OTHER 933.8 MB
NONO-2.fastq.gz OTHER 1.6 GB
NONO-2.fastq.gz OTHER 1.6 GB
PSF-1.fastq.gz OTHER 2.2 GB
PSF-1.fastq.gz OTHER 2.2 GB
PSF-2.fastq.gz OTHER 1.5 GB
PSF-2.fastq.gz OTHER 1.5 GB
siGFP-1.fastq.gz ncRNA-Seq 57.9 MB
siGFP-1.fastq.gz ncRNA-Seq 57.9 MB
siGFP-2.fastq.gz ncRNA-Seq 776.7 MB
siGFP-2.fastq.gz ncRNA-Seq 776.7 MB
siNEAT1-1.fastq.gz ncRNA-Seq 860.8 MB
siNEAT1-1.fastq.gz ncRNA-Seq 860.8 MB
siNEAT1-2.fastq.gz ncRNA-Seq 804.7 MB
siNEAT1-2.fastq.gz ncRNA-Seq 804.7 MB
siNEAT1_V2-1.fastq.gz ncRNA-Seq 170.2 MB
siNEAT1_V2-1.fastq.gz ncRNA-Seq 170.2 MB
siNEAT1_V2-2.fastq.gz ncRNA-Seq 1017.0 MB
siNEAT1_V2-2.fastq.gz ncRNA-Seq 1017.0 MB
siNONO-1.fastq.gz ncRNA-Seq 343.5 MB
siNONO-1.fastq.gz ncRNA-Seq 343.5 MB
siNONO-2.fastq.gz ncRNA-Seq 1.2 GB
siNONO-2.fastq.gz ncRNA-Seq 1.2 GB
siPSF-1.fastq.gz ncRNA-Seq 462.8 MB
siPSF-1.fastq.gz ncRNA-Seq 462.8 MB
siPSF-2.fastq.gz ncRNA-Seq 527.0 MB
siPSF-2.fastq.gz ncRNA-Seq 527.0 MB
siPSPC1-1.fastq.gz ncRNA-Seq 374.6 MB
siPSPC1-1.fastq.gz ncRNA-Seq 374.6 MB
siPSPC1-2.fastq.gz ncRNA-Seq 606.9 MB
siPSPC1-2.fastq.gz ncRNA-Seq 606.9 MB

Analysis Pipelines (1)

GSE90650 CLIP-seq Data Processing 6 steps
CLIP-seq geo_data_processing GSE90650