Abstract
Recent analyses have revealed many functional microRNA (miRNA) targets in mammalian protein coding regions. But, the mechanisms that ensure miRNA function when their target sites are located in protein coding regions of mammalian mRNA transcripts are largely unknown. In this paper, we investigate some potential biological factors, such as target site accessibility and local translation efficiency. We computationally analyze these two factors using experimentally identified miRNA targets in human protein coding region. We find site accessibility is significantly increased in miRNA target region to facilitate miRNA binding. At the mean time, local translation efficiency is also selectively decreased near miRNA target region. GC-poor codons are preferred in the flank region of miRNA target sites to ease the access of miRNA targets. Within-genome analysis shows substantial variations of site accessibility and local translation efficiency among different miRNA targets in the genome. Further analyses suggest target gene’s GC content and conservation level could explain some of the differences in site accessibility. On the other hand, target gene’s functional importance and conservation level can affect local translation efficiency near miRNA target region. We hence propose both site accessibility and local translation efficiency are important in miRNA action when miRNA target sites are located in mammalian protein coding regions.
Highlights
MiRNAs are a class of small non-coding RNAs that regulate gene expression in post-transcriptional stage [1]
To investigate the biological basis of miRNA action when miRNA targets are located in protein coding region of mammalian transcripts, we have performed a genome scale analysis of site accessibility and translation efficiency near miRNA target region in the human genome
We have found both site accessibility and translation efficiency is selectively varied in the flank region of miRNA target sites (Figures 1 and 2)
Summary
MiRNAs are a class of small non-coding RNAs that regulate gene expression in post-transcriptional stage [1]. Most miRNA target sites are located in protein coding region of target gene. Two recent studies have investigated the reason why mammalian miRNA target sites are restricted to the 39-UTR of mRNA transcripts [3,4]. They have suggested active mRNA translation may impede miRNA association with target mRNAs in mammalian genomes [3,4]. Increasing evidences have confirmed many functional miRNA target sites are located in protein coding region of mammalian mRNA transcripts as well [5,6,7,8,9,10,11,12]. Given the prevalence of miRNA target sites occurred in mammalian protein coding sequences, it is important to investigate biological factors that may affect miRNA action when their targets are located in mammalian protein coding regions
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