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Letter

Genomic localization of RNA binding proteins reveals links between pre-mRNA processing and transcription

¹ Department of Systems Biology, Harvard Medical School, Boston, Massachusetts 02115, USA; ² Departments of Biostatistics and Computational Biology, The Dana-Farber Cancer Institute and Harvard School of Public Health, Boston, Massachusetts 02115, USA; ³ Department of Cancer Biology, The Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA

Pre-mRNA processing often occurs in coordination with transcription thereby coupling these two key regulatory events. As such, many proteins involved in mRNA processing associate with the transcriptional machinery and are in proximity to DNA. This proximity allows for the mapping of the genomic associations of RNA binding proteins by chromatin immunoprecipitation (ChIP) as a way of determining their sites of action on the encoded mRNA. Here, we used ChIP combined with high-density microarrays to localize on the human genome three functionally distinct RNA binding proteins: the splicing factor polypyrimidine tract binding protein (PTBP1/hnRNP I), the mRNA export factor THO complex subunit 4 (ALY/THOC4), and the 3' end cleavage stimulation factor 64 kDa (CSTF2). We observed interactions at promoters, internal exons, and 3' ends of active genes. PTBP1 had biases toward promoters and often coincided with RNA polymerase II (RNA Pol II). The 3' processing factor, CSTF2, had biases toward 3' ends but was also observed at promoters. The mRNA processing and export factor, ALY, mapped to some exons but predominantly localized to introns and did not coincide with RNA Pol II. Because the RNA binding proteins did not consistently coincide with RNA Pol II, the data support a processing mechanism driven by reorganization of transcription complexes as opposed to a scanning mechanism. In sum, we present the mapping in mammalian cells of RNA binding proteins across a portion of the genome that provides insight into the transcriptional assembly of RNA–protein complexes.

⁵ Corresponding authors.

E-mail Pamela_Silver{at}hms.harvard.edu; fax (401) 863-9653.

E-mail Alexander_Brodsky{at}brown.edu; fax (401) 863-9653.

[Supplemental material is available online at www.genome.org and http://silver.med.harvard.edu/brodsky/.]

Article published online before print. Article and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.5211806

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