Snipper, an Eri1 homologue, affects histone mRNA abundance and is crucial for normal Drosophila melanogaster development

Abstract

The conserved 3'-5' RNA exonuclease ERI1 is implicated in RNA interference inhibition, 5.8S rRNA maturation and histone mRNA maturation and turnover. The single ERI1 homologue in Drosophila melanogaster Snipper (Snp) is a 3'-5' exonuclease, but its in vivo function remains elusive. Here, we report Snp requirement for normal Drosophila development, since its perturbation leads to larval arrest and tissue-specific downregulation results in abnormal tissue development. Additionally, Snp directly interacts with histone mRNA, and its depletion results in drastic reduction in histone transcript levels. We propose that Snp protects the 3'-ends of histone mRNAs and upon its absence, histone transcripts are readily degraded. This in turn may lead to cell cycle delay or arrest, causing growth arrest and developmental perturbations.

ERI1: A case report of an autosomal recessive syndrome associated with developmental delay and distal limb abnormalities

“…In addition, heterozygous Eri1 ‐ knockout mice show skeletal anomalies with 80% of the mice developing an additional rib pair (Rath, 2010). In other model organisms such as C. elegans (Le et al, 2016) and Drosophila (Alexiadis et al, 2017), ERri1 is ubiquitously expressed at various stages and tissues. Low levels of Snipper , the Drosophila Eri1 homolog lead to developmental arrest or tissue malformation (Alexiadis et al, 2017).…”

“…In other model organisms such as C. elegans (Le et al, 2016) and Drosophila (Alexiadis et al, 2017), ERri1 is ubiquitously expressed at various stages and tissues. Low levels of Snipper , the Drosophila Eri1 homolog lead to developmental arrest or tissue malformation (Alexiadis et al, 2017). Moreover, expressing Eri1 knockout in a tissue‐specific manner showed different phenotypes, such as perturbation of normal ommatidia arrangement in the eye and adventitious antenna‐like structures or bristles (Alexiadis et al, 2017).…”

“…A study on C. elegans , has suggested that maternal ERri1 , but not paternal, is sufficient for proper tissue homogeneity and suppression of cell‐to‐cell variations (Le et al, 2016). In addition, the Drosophila Eri1 homolog, Snipper , is maternally provided (Alexiadis et al, 2017) and its absence leads to lethality. Similar lethality levels were also observed in Eri1 knockout mice, with less than 10% of these animals surviving to weaning age (Ansel et al, 2008).…”

“…Low levels of Snipper, the Drosophila Eri1 homolog lead to developmental arrest or tissue malformation (Alexiadis et al, 2017). Moreover, expressing Eri1 knockout in a tissue-specific manner showed different phenotypes, such as perturbation of normal ommatidia arrangement in the eye and adventitious antennalike structures or bristles (Alexiadis et al, 2017). Taken together, F I G U R E 2 X-rays of the patient's extremities showed multiple congenital anomalies of hands and feet: (a) left hand-foreshortened middle phalanx of the fifth digit with mild radial curvature.…”

“…Interestingly, in C. elegans , while Eri1 inhibits the abundance of some RNAi, it can also act as a promoter of some endo‐siRNAs, suggesting that cross‐modulatory interactions among silencing processes exist (Bian et al, 2011; Kennedy et al, 2004; Lee et al, 2006). In addition to its role in regulatory RNA pathways, Eri1 is crucial for processing of the 5.8S ribosomal RNA (rRNA) and regulation of histone proteins during the cell cycle (Alexiadis et al, 2017; Ansel et al, 2008; Hoefig et al, 2013; Yang et al, 2006).…”