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Protein–RNA interactions: new genomic technologies and perspectives

An Erratum to this article was published on 31 January 2012

This article has been updated

Abstract

RNA-binding proteins are key players in the regulation of gene expression. In this Progress article, we discuss state-of-the-art technologies that can be used to study individual RNA-binding proteins or large complexes such as the ribosome. We also describe how these approaches can be used to study interactions with different types of RNAs, including nascent transcripts, mRNAs, microRNAs and ribosomal RNAs, in order to investigate transcription, RNA processing and translation. Finally, we highlight current challenges in data analysis and the future steps that are needed to obtain a quantitative and high-resolution picture of protein–RNA interactions on a genome-wide scale.

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Figure 1: Comparison of HITS-CLIP and its latest variants, PAR-CLIP and iCLIP.
Figure 2: Ribonomic methods to study transcription and translation.
Figure 3: Identification of binding sites and normalization.

Change history

  • 31 January 2012

    In two instances in the same sentence of the above article, the use of 'mRNA' and 'microRNA (miRNA)' had been reversed. The sentence has now been corrected so that it reads: “Although the direct pairing of an miRNA with its target mRNA cannot yet be deduced from these data, the detection of Argonaute binding sites in both miRNAs and mRNAs enabled the discovery of endogenous mRNA target sites.” The editors apologize for this error.

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Acknowledgements

This work was supported by the Medical Research Council, the European Molecular Biology Laboratory (grant number U105185858), the European Research Council (206726-CLIP) and by a Human Frontiers Science Program Long-Term fellowship and an EMBL EIPOD fellowship to J.K. and K.Z., respectively.

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Correspondence to Jernej Ule.

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The authors declare no competing financial interests.

Related links

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FURTHER INFORMATION

Nicholas M. Luscombe's homepage

Jernej Ule's homepage

CLIP forum

CLIPZ

GSNAP

iCLIP questions and answers

iCount pipeline

Novoalign

Segemehl

starBase

Uwe Ohler's Research Group PARalyzer (PAR-CLIP data analyzer)

Glossary

Argonaute proteins

Core components of the RNA-mediated silencing pathways. They provide the platform for target mRNA recognition by small non-coding RNAs and harbour the catalytic activity for mRNA cleavage.

Differential display

A PCR-based approach that was used to study differences in RNA populations. It has now been superseded by microarray and RNA sequencing approaches.

Global run-on sequencing

(GRO-seq). A technique that combines nuclear run-on assays with high-throughput sequencing to obtain genome-wide information about active transcription.

Heterogeneous nuclear ribonucleoprotein

(HNRNP). The core protein components of heterogeneous nuclear ribonucleoprotein particles that associate with all nascent transcripts. They are involved in diverse aspects of post-transcriptional regulation.

k-mers

Nucleic acid sequences with a number of nucleotides of length k.

NOVA

A regulator of a biologically coherent set of RNAs important for synaptic function. It is involved in the neurological disorder paraneoplastic opsoclonus myoclonus ataxia.

Ribonomics

The genome-scale study of protein–RNA interactions and their functional consequences.

Ribonucleoprotein particles

(RNPs). Complexes consisting of protein and RNA components.

Small nuclear RNAs

(snRNAs). A class of non-coding RNAs that are found in the nucleus of eukaryotic cells and that constitute core components of all subunits of the spliceosome.

Small nucleolar RNAs

(snoRNAs). A class of small non-coding RNAs that are involved in guiding chemical modifications of other RNAs, such as ribosomal or transfer RNAs.

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König, J., Zarnack, K., Luscombe, N. et al. Protein–RNA interactions: new genomic technologies and perspectives. Nat Rev Genet 13, 77–83 (2012). https://doi.org/10.1038/nrg3141

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