Identification and Characterization of a Novel Non-Coding RNA Involved in Sperm Maturation

Abstract

A long and ever-expanding roster of small (∼20–30 nucleotides) RNAs has emerged during the last decade, and most can be subsumed under the three main headings of microRNAs(miRNAs), Piwi-interacting RNAs(piRNAs), and short interferingRNAs(siRNAs). Among the three categories, miRNAs is the most quickly expanded group. The most recent number of identified miRNAs is 16,772 (Sanger miRbase, April 2011). However, there are insufficient publications on their primary forms, and no tissue-specific small RNAs precursors have been reported in the epididymis. Here, we report the identification in rats of an epididymis-specific, chimeric, noncoding RNA that is spliced from two different chromosomes (chromosomes 5 and 19), which we named HongrES2. HongrES2 is a 1.6 kb mRNA-like precursor that gives rise to a new microRNA-like small RNA (mil-HongrES2) in rat epididymis. The generation of mil-HongrES2 is stimulated during epididymitis. An epididymis-specific carboxylesterase named CES7 had 100% cDNA sequence homology at the 3′end with HongrES2 and its protein product could be downregulated by HongrES2 via mil-HongrES2. This was confirmed in vivo by initiating mil-HongrES2 over-expression in rats and observing an effect on sperm capacitation.

Critical roles of long noncoding RNAs in Drosophila spermatogenesis

“…However, it remains unclear whether lncRNAs are truly involved in male reproduction in vivo. Three mouse lncRNAs are involved in spermatogenesis in vitro Ni et al 2011;Arun et al 2012), but the aforementioned Pldi RNA represents the only case in which functional significance in spermatogenesis has been demonstrated in lncRNA knockout models (Heinen et al 2009). Thus, we attempted to survey the functional roles of lncRNAs in spermatogenesis using our optimized CRISPR system.…”

Long noncoding RNAs in spermatogenesis: insights from recent high-throughput transcriptome studies

“…lncRNAs are suggested to increase the proximity of those proteins to their reaction sites, thus enhancing the rate of reactions such as DNA methylation and histone modifications. Finally, lncRNAs can be processed by certain RNase such as Drosha and Dicers to form shorter RNAs, which in turn may carry out further post-transcriptional regulation-examples include H19 (Keniry et al 2012) and HongrES2 (Ni et al 2011).…”

“…HongrES2 is a 1588-bp lncRNA and expressed specifically in the cauda region of epididymis (Ni et al 2011).…”

“…Moreover, overexpression of mil-HongrES2 results in retarded sperm capacitation as indicated by the global tyrosine phosphorylation level (Ni et al 2011), suggesting that an endogenous low level of the lncRNA expression is a gatekeeper for normal sperm maturation process in epididymis.…”

Makings of the Best Spermatozoa: Molecular Determinants of High Fertility

“…CES7 is a carboxylesterase with cholesterol esterase activity, which is necessary during sperm capacitation process. Also, tyrosine phosphorylation of the sperm protein during capacitation was affected by high expression of this microRNA-like small RNA indicating the requisite of low level expression for normal sperm maturation process in epididymis (Ni et al, 2011). In summary, although there exist significant numbers of lncRNAs in the body, their expression dynamics and functions in sperm are not well studied.…”