LENG8 mediates RNA nuclear retention and degradation in eukaryotes.

Area of Science:

• Molecular Biology
• RNA Biology
• Cellular Quality Control

Background:

• Eukaryotic cells retain incompletely processed RNAs in the nucleus, but the mechanisms are unclear.
• RNA quality control is essential for preventing aberrant molecules from interfering with cellular processes.

Purpose of the Study:

• To identify novel factors involved in nuclear RNA retention and degradation.
• To elucidate the molecular mechanisms of RNA quality control in eukaryotes.

Main Methods:

• Identification of LENG8 as an RNA binding protein.
• Co-immunoprecipitation assays to identify interacting partners.
• Analysis of RNA export in LENG8-depleted cells.
• Investigating interactions with the RNA exosome pathway.

Main Results:

• LENG8 acts as a conserved RNA nuclear retention and degradation factor.
• LENG8 is recruited to pre-mRNAs by splicing factors like U1 snRNP.
• LENG8 forms the REX complex with PCID2 and SEM1, inhibiting mRNA export.
• Loss of LENG8 leads to cytoplasmic leakage of misprocessed RNAs.
• LENG8 promotes nuclear RNA degradation via interaction with PAXT and the RNA exosome.

Conclusions:

• LENG8 is a key component of a conserved nuclear RNA quality control pathway.
• This pathway ensures the fidelity of RNA export by retaining and degrading aberrant RNAs.
• The findings reveal a novel mechanism for preventing the accumulation of non-functional RNA species in the cytoplasm.