Distinct and Modular Organization of Protein Interacting Sites in Long Non-coding RNAs.

Shrey Gandhi,Saakshi Jalali,Vinod Scaria

doi:10.3389/fmolb.2018.00027

Abstract

Background: Long non-coding RNAs (lncRNAs), are being reported to be extensively involved in diverse regulatory roles and have exhibited numerous disease associations. LncRNAs modulate their function through interaction with other biomolecules in the cell including DNA, RNA, and proteins. The availability of genome-scale experimental datasets of RNA binding proteins (RBP) motivated us to understand the role of lncRNAs in terms of its interactions with these proteins. In the current report, we demonstrate a comprehensive study of interactions between RBP and lncRNAs at a transcriptome scale through extensive analysis of the crosslinking and immunoprecipitation (CLIP) experimental datasets available for 70 RNA binding proteins.Results: Our analysis suggests that density of interaction sites for these proteins was significantly higher for specific sub-classes of lncRNAs when compared to protein-coding transcripts. We also observe a positional preference of these RBPs across lncRNA and protein coding transcripts in addition to a significant co-occurrence of RBPs having similar functions, suggesting a modular organization of these elements across lncRNAs.Conclusion: The significant enrichment of RBP sites across some lncRNA classes is suggestive that these interactions might be important in understanding the functional role of lncRNA. We observed a significant enrichment of RBPs which are involved in functional roles such as silencing, splicing, mRNA processing, and transport, indicating the potential participation of lncRNAs in such processes.

Highlights

Long non-coding RNAs, are being reported to be extensively involved in diverse regulatory roles and have exhibited numerous disease associations
We analyzed publicly available datasets for 70 RNA binding proteins derived from seven datasets encompassing five technologies viz. PAR-crosslinking and immunoprecipitation (CLIP), HITS-CLIP, individual-nucleotide resolution Cross-Linking and Immuno Precipitation (iCLIP), RNA Immunoprecipitation sequencing (RIP-seq), and cross-linking ligation and sequencing of hybrids (CLASH)
The interactions between proteins and RNA molecules can provide the essential insights into the functioning of the long non-coding RNA (lncRNA)

Summary

Introduction

Long non-coding RNAs (lncRNAs), are being reported to be extensively involved in diverse regulatory roles and have exhibited numerous disease associations. We demonstrate a comprehensive study of interactions between RBP and lncRNAs at a transcriptome scale through extensive analysis of the crosslinking and immunoprecipitation (CLIP) experimental datasets available for 70 RNA binding proteins. The recent years have seen the discovery of a large number of novel transcripts which belong to the long non-coding RNA (lncRNA) class in humans and other model organisms (Pauli et al, 2012). This has been largely contributed by the availability of high-throughput methodologies for transcriptome annotation, including tiling microarrays (Hafner et al, 2010a; Furey, 2012) and deep sequencing (Roberts et al, 2011).

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Discussion

Conclusion