Rtl8a (retrotransposon Gag-like protein 8A; Cxx1 family) is one of a cluster of three near-identical X-linked mouse paralogs (Rtl8a/8b/8c) domesticated from a Ty3/gypsy sushi-ichi-related LTR retrotransposon. Mouse Rtl8a and Rtl8b encode identical 113-residue proteins corresponding to a single truncated retroviral Gag capsid (CA)-like domain; they carry a rodent-specific N-terminal nuclear-localization-signal-like sequence and lack any catalytic domain. mRTL8A/8B localize to the nucleus (nucleoli) and, in prefrontal-cortex neurons, to both nucleus and cytoplasm, and are expressed in the prefrontal cortex and hypothalamus. By conservation with human RTL8 they act as capsid-derived adaptors linking the retroelement capsid protein PEG10 to the proteasome shuttle factor UBQLN2. Rtl8a/Rtl8b double-knockout mice develop late-onset obesity, reduced social response and apathy-like behaviour with reduced GABA-A receptor subunit (GABRB2) expression, resembling features of Prader-Willi syndrome, indicating an important brain function with a gene-dosage effect.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005634 nucleus | IDA PMID:39875098 Targeting of retrovirus-derived Rtl8a/8b causes late-onset o... | NEW | Summary: mRTL8A/8B localize to nuclei (nucleoli) by immunofluorescence and to both nucleus and cytoplasm in prefrontal-cortex neurons; they carry a rodent-specific N-terminal NLS-like sequence. Reason: Not in GOA (the gene currently has no annotations). Direct mouse localization data support a nuclear location, consistent with the human RTL8 nucleolar localization. Supporting Evidence: PMID:39875098 the former in the nuclei (nucleoli) and the latter in the cytoplasm PMID:39875098 these proteins are localized in both the nucleus (indicated by arrows) and cytoplasm of neurons |
| GO:0030674 protein-macromolecule adaptor activity | ISS PMID:40680123 Endogenous retrovirus-like proteins recruit UBQLN2 to stress... | NEW | Summary: By conservation with human RTL8, which bridges the retroelement capsid protein PEG10 and the proteasome shuttle factor UBQLN2; the murine RTL8 ortholog participates in the UBQLN2 proteostasis network. Reason: Not in GOA. The adaptor function is strongly conserved across the near-identical RTL8 proteins; human RTL8 binds the PEG10 capsid and UBQLN2 and confers on UBQLN2 the ability to complex with and regulate PEG10. Proposed as the mouse protein's molecular function. Supporting Evidence: PMID:40680123 RTL8 confers on UBQLN2 the ability to complex with and regulate PEG10 PMID:39775359 RTL8 bound to the N-terminal domain of PEG10 capsid PMID:35247097 confirmed the interaction between UBQLN2 and RTL8 both in vitro using recombinant proteins and in vivo using mouse brain tissue |
| GO:1900182 positive regulation of protein localization to nucleus | ISS PMID:35247097 RTL8 promotes nuclear localization of UBQLN2 to subnuclear c... | NEW | Summary: Conserved with human RTL8, which promotes nuclear translocation of UBQLN2; mouse RTL8A/8B carry a nuclear-localization signal and localize to nuclei. Reason: Not in GOA. Proposed by conservation with the human RTL8 function; RTL8 itself performs the recruiting step (binds UBQLN2 and drives its nuclear translocation). Supporting Evidence: PMID:35247097 RTL8 promotes nuclear translocation of UBQLN2 |
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Download this section (compressed HTML)Q: Are mouse Rtl8a and Rtl8b (identical proteins) functionally redundant, and how does their loss cause obesity and altered social/apathy behaviour?
Experiment: Test PEG10 and UBQLN2 handling in Rtl8a/8b double-knockout neurons, and rescue with wild-type versus adaptor-dead RTL8; relate to GABRB2 expression and the obesity/behaviour phenotype.
Hypothesis: Mouse RTL8A/8B act via the conserved PEG10/UBQLN2 proteostasis axis in brain.
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