Cap-seq reveals complicated miRNA transcriptional mechanisms in C. elegans and mouse

Abstract

Background: MicroRNAs (miRNAs) regulate target gene expression at post-transcriptional level. Intense research has been conducted for miRNA identification and the target finding. However, much less is known about the transcriptional regulation of miRNA genes themselves. Recently, a special group of pre-miRNAs that are produced directly by transcription without Drosha processing were validated in mouse, indicating the complexity of miRNA biogenesis.

Methods: In this work, we detect clusters of aligned Cap-seq reads to find the transcription start sites (TSSs) for intergenic miRNAs and study their transcriptional regulation in Caenorhabditis elegans and mouse.

Results: In both species, we have identified a class of special pre-miRNAs whose 5′ ends are capped, and are most probably generated directly by transcription. Furthermore, we distinguished another class of special pre-miRNAs that are 5′-capped but are also part of longer primary miRNAs, suggesting they may have more than one transcription mechanism. We detected multiple cap reads peaks within miRNA clusters in C. elegans. We surmised that the miRNAs in a cluster may either be transcribed independently or be re-capped during the microprocessor cleavage process. We also observed that H3K4me3 and Pol II are enriched at those identified miRNA TSSs.

Conclusions: The Cap-seq datasets enabled us to annotate the primary TSSs for miRNA genes with high resolution. Special class of 5′-capped pre-miRNAs have been identified in both C. elegans and mouse. The capping patter of miRNAs in a cluster indicate that clustered miRNA transcripts probably undergo a re-capping procedure during the microprocessor cleavage process.

Graphical abstract

Keywords

miRNA / Cap-seq / transcriptional regulation

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SUPPLEMENTARY MATERIALS

The supplementary materials can be found online with this article at DOI 10.1007/s40484-017-0123-4.

ACKNOWLEDGEMENTS

We thank David Arnosti for critical discussions and helpful comments on the manuscript. We are also grateful to Weifeng Gu, Ron Chen, and Mingyi Xie for providing the explicit explanations to questions related to 5′-capped pre-miRNAs and 5′ recessed RNAs. This work was supported by NSF CAREER Grant DBI-0953738.

COMPLIANCE WITH ETHICS GUIDELINES

The authors Jiao Chen, Dongxiao Zhu, and Yanni Sun declare they have no conflict of interests. All the data sets the authors used are from public repositories.

RIGHTS & PERMISSIONS

2017 Higher Education Press and Springer-Verlag GmbH Germany