Abstract
Due to the abundance and conserved role of tRNAs, fragments thereof were considered as mere degradation products for a long time. Lately, however, it was unveiled that these 15â35 nucleotides-long tRNA (-precursor) -derived small RNAs (tsRNAs) can modulate gene expression by different mechanisms and act in a variety of contexts. While some tsRNAs inhibit translation globally by impeding the formation of the translation initiation complex, many studies find tsRNAs to silence target genes in a sequence-specific manner that is potentially mediated by Argonaute proteins. This function plays a role in transposon control, but was also found to be exploited by viruses and trypanosoma to regulate host genes. Beyond their involvement in infectious disease, aberrant tsRNA expression is linked to several other diseases such as cancer or neurological disorders. Furthermore, it was recently shown that tsRNAs residing in sperm of high-fat or low-protein diet mice can act as transgenerational transmitters that induce metabolic disorders and addictive behavior in the offspring. A better understanding of tsRNA-mediated gene regulation pathways, will not only expand our knowledge on how parental lifestyle influences the epigenome of the progeny, but may also enable the development of new drugs and biomarkers.
Highlights
Small Non-Coding RNAsA major advance in understanding gene expression was the discovery of regulatory non-coding RNAs. ncRNAs are transcripts that, unlike messenger RNA, do not code for proteins
As tRNAderived small RNA (tsRNA) were very recently shown to be important players in transgenerational epigenetics of metabolic disorders and addiction behavior, we focus especially on their role in disease
Contrasting conclusions were drawn by Yeung et al, who found high levels of a 18 nt 3′ tsRNA (3′ tsRNA-Lys; confirmed by Northern Blot analysis) in human immunodeficiency virus type 1 (HIV-1) infected MT4 T-cells [81]. 3′ tsRNA-Lys is antisense to the primer binding site (PBS) of the HIV-1. As they saw this 3′ tsRNA to be associated with AGO2, they suggested that 3′ tsRNA-Lys directs an RNA interference (RNAi)-based defense mechanism of the host against HIV-1
Summary
Small Non-Coding RNAsA major advance in understanding gene expression was the discovery of regulatory non-coding RNAs (ncRNAs). ncRNAs are transcripts that, unlike messenger RNA (mRNAs), do not code for proteins. They observed that a specific set of 5′ tRHs (30–35 nt) that is generated independently of Angiogenin is enriched during retinoic acid induced differentiation of mouse embryonic stem cells (confirmed by Northern Blot analysis).
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