microRNAs and other non-coding RNAs

Note: In this section, we currently show the abstract of an unpublished manuscript only.
We are planning to provide more detailed methods and results regardless of the status of publication.

MicroRNAs affect gene expression by targeting cis-transcribed non-coding RNAs

Takay Saito¹, Even Skaland¹, Pål Sætrom^1,2

¹Department of Cancer Research and Molecular Medicine,
Norwegian University of Science and Technology, NO-7489 Trondheim, Norway
²Department of Computer and Information Science,
Norwegian University of Science and Technology, NO-7491 Trondheim, Norway

Abstract

Background

MicroRNAs (miRNAs) have a well-documented role in regulating genes post transcription, but studies have also reported that some miRNAs can regulate transcription. This transcriptional regulation involves non-coding RNAs (ncRNAs) overlapping or interacting with the target gene promoter, suggesting that ncRNAs overlapping protein-coding genes and forming complex loci may be important miRNA targets. Here, we have investigated miRNAs’ potential to regulate two such classes of complex loci: cis natural antisense (cis-NATs) ncRNAs and chromatin-associated RNAs (CARs).

Results

Resampling tests revealed that mRNAs overlapping cis-NATs and CARs tend to have longer and more conserved 3’UTRs than random genes and that the cis-NATs and CARs themselves are enriched with conserved miRNA target sites. Photoactivatable-Ribonucleoside-Enhanced Crosslinking and Immunoprecipitation (PAR-CLIP) data confirmed several miRNA binding sites in these complex loci ncRNAs. Moreover, similar to PAR-CLIP target sites in 3’UTRs, but in contrast to sites in 5’UTRs and CDS, these ncRNA sites were strong and highly conserved. Correlation analyses of miRNA and mRNA expression profiles further showed that miRNA targeting of cis-NATs and intronic CARs, similar to 3’UTRs, have a negative effect on host mRNA expression.

Conclusions

Complex loci containing non-coding cis-NATs or CARs appear to be under strong miRNA regulation. Not only do miRNAs tend to target coding RNAs in complex more than other coding RNAs, but both sequence conservation and PAR-CLIP data show that miRNAs also target the complex loci ncRNAs. Indeed, expression data suggest that miRNA-targeting of non-coding cis-NATs and intronic CARs have a strong impact on host gene expression.