Superabundant microRNAs are transcribed from human rDNA spacer promoters insulated by CTCF

TL;DR

This study discovers that certain microRNAs are transcribed from human ribosomal DNA and may act as cancer biomarkers due to their rapid export and presence in exosomes.

Contribution

The paper identifies a novel transcription mechanism for miR-1275 and miR-6724 from rDNA spacer promoters insulated by CTCF.

Findings

miR-1275 and miR-6724 are transcribed from rDNA spacer promoters with high RNA polymerase II activity.

These microRNAs are rapidly exported and detected in exosomes as potential cancer biomarkers.

CTCF insulates the miR-1275/miR-6724 transcription unit within a 400-bp span of the rDNA spacer promoter.

Abstract

microRNAs are ~22-nucleotide RNAs processed from primary transcripts and exported from the nucleus to repress gene expression by base-pairing to mRNAs. Unexpectedly, we find that the highest levels of RNA polymerase II (Pol II) at human microRNA genes are within the ribosomal gene repeat arrays (rDNAs). Alignment of public nascent transcript data to the hs1 human genome assembly reveals a 50-nucleotide transcript for both miR-1275 and miR-6724, which exits from the nucleus with exceptional rapidity. We show that the miR-1275/miR-6724 transcription unit is closely flanked by CCCTC-binding factor (CTCF) within a <400-bp span of the rDNA spacer promoter. miR-1275/miR-6724 and microRNA precursors expressed from the 5′ external transcribed spacer (5′ETS) are exported independently of known RNA processing activities and are detected in exosomes and as circulating cancer biomarkers. We propose that the rDNA spacer promoter and 5′ETS microRNA genes have evolved for general regulatory functions in recipient cells.

microRNAs are transcribed from the spacer promoters of human ribosomal RNA genes and detected as circulating cancer biomarkers.

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