The secreted endoribonuclease ENDU-2 from the soma protects germline immortality in C. elegans

Abstract

Multicellular organisms coordinate tissue specific responses to environmental information via both cell-autonomous and non-autonomous mechanisms. In addition to secreted ligands, recent reports implicated release of small RNAs in regulating gene expression across tissue boundaries. Here, we show that the conserved poly-U specific endoribonuclease ENDU-2 in C. elegans is secreted from the soma and taken-up by the germline to ensure germline immortality at elevated temperature. ENDU-2 binds to mature mRNAs and negatively regulates mRNA abundance both in the soma and the germline. While ENDU-2 promotes RNA decay in the soma directly via its endoribonuclease activity, ENDU-2 prevents misexpression of soma-specific genes in the germline and preserves germline immortality independent of its RNA-cleavage activity. In summary, our results suggest that the secreted RNase ENDU-2 regulates gene expression across tissue boundaries in response to temperature alterations and contributes to maintenance of stem cell immortality, probably via retaining a stem cell specific program of gene expression.

Integrative meta‑analysis of gene expression profiles identifies FEN1 and ENDOU as potential diagnostic biomarkers for cervical squamous cell carcinoma

“…ENDOU was also reported to regulate c-Myc expression, cell proliferation and nucleotide metabolism via fine-tuning of mRNA stability in tumor cells (40,41,70,71). The previously indicated selective cytotoxicity of ENDOU against tumor cells (39,40,81,82) and its deregulation in cervical carcinogenesis observed in the present study may indicate the potential benefits of its pharmacological modulation in patients with cervical carcinoma. Similarly, the results of the present study demonstrated that cervical tumors with low ENDOU expression were characterized by the molecular phenotype associated with poorer differentiation, as well as perturbation in certain pathways, including transcriptional regulation in cancer, growth factor and kinase signaling.…”

Protection of germline immortality by the soma via a secreted endoribonuclease

“…Here we outline our recent findings about protection and maintenance of germline immortality by the soma via secretion of the endoribonuclease ENDU-2 in C. elegans. [8] We found that ENDU-2 binds to mRNA and affects abundance of transcripts in -both soma and germline. Based on these findings we propose that ENDU-2 confers a non-cell-autonomous mechanism to control gene expression across tissue boundaries, thus mediating soma-to-germline communication.…”

Molecular physiology regulating cold tolerance and acclimation of <i>Caenorhabditis elegans</i>

“…33) In the report by Qi et al, endu-2 is mainly expressed in intestinal cells. 33) Then, the secreted RNase ENDU-2 from intestinal cells may non-autonomously affects ADL thermosensitivity.…”

“… 30 ) Qi et al recently noted that RNase ENDU-2 behaves as a secretory protein, and that the secretion signal peptide comprised of the first 19 amino acids in ENDU-2 is essential for this phenomenon. 33 ) Although the detailed molecular machinery involved in ENDU-2 secretion, such as packaging in exosomes or lysosomes, is unclear, ENDU-2 has been shown to be taken up by tissues other than the expressing cells. 33 ) In the report by Qi et al , endu-2 is mainly expressed in intestinal cells.…”

“… 33 ) Although the detailed molecular machinery involved in ENDU-2 secretion, such as packaging in exosomes or lysosomes, is unclear, ENDU-2 has been shown to be taken up by tissues other than the expressing cells. 33 ) In the report by Qi et al , endu-2 is mainly expressed in intestinal cells. 33 ) Then, the secreted RNase ENDU-2 from intestinal cells may non-autonomously affects ADL thermosensitivity.…”