ENAapplication/xmlftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR124/002/SRR1240812/SRR1240812.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR124/009/SRR1240809/SRR1240809_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR124/008/SRR1240808/SRR1240808_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR124/007/SRR1240817/SRR1240817.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR124/000/SRR1240810/SRR1240810_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR124/004/SRR1240814/SRR1240814.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR124/007/SRR1240807/SRR1240807_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR124/001/SRR1240811/SRR1240811_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR124/008/SRR1240808/SRR1240808_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR124/009/SRR1240809/SRR1240809_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR124/007/SRR1240807/SRR1240807_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR124/001/SRR1240811/SRR1240811_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR124/000/SRR1240810/SRR1240810_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR124/006/SRR1240816/SRR1240816.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR124/005/SRR1240815/SRR1240815.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR124/003/SRR1240813/SRR1240813.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR124/008/SRR1240818/SRR1240818.fastq.gzprimaryOK200GenomicsComputational Biology, Max Planck Institute for Molecular Geneticshttps://www.ebi.ac.uk/ena/browser/view/PRJNA244784Homo sapiensxref:PubMed:28250203xref:PubMed:25310978Microprocessor is responsible for conversion of pri-miRNA transcripts into pre-miRNA hairpins in miRNA biogenesis. The in vivo properties of this process remain enigmatic. Here, we present the first study of in vivo transcriptome-wide pri-miRNA processing using next-generation sequencing of chromatin-associated pri-miRNAs. We identify a distinctive Microprocessor signature in the transcriptome profile, from which efficiency of the endogenous processing event can be accurately quantified. This analysis reveals differential susceptibility to Microprocessor cleavage as a key regulatory step in miRNA biogenesis. Processing is highly variable among pri-miRNAs and a better predictor of miRNA abundance than primary transcription itself. Processing is also largely stable across three cell lines, suggesting a major contribution of sequence determinants. Based on differential processing efficiencies we define functionality for short sequence features adjacent to the pre-miRNA hairpin. In conclusion, we identify Microprocessor as the main hub for diversified miRNA output and suggest a role for uncoupling miRNA biogenesis from host gene expression. Overall design: We performed polyA independent deep sequencing of the chromatin-isolated RNA fraction for 5 samples: 2 replicates in HeLa cells, 1 Drosha knock down in HeLa cells, 1 sample for A549 cells and 1 sample for HEK293 cells. We also performed deep sequencing of the small RNA fraction in the same cell lines.ENAfalseHomo sapiensGenome-wide quantification of microRNA processing efficiency from RNA-seq data2025-09-242014-04-21PRJNA244784GSE5686296062825020325310978