LENG8 mediates RNA nuclear retention and degradation in eukaryotes

In eukaryotes, incompletely and aberrantly processed mRNAs as well as numerous noncoding RNAs are retained in the nucleus and often degraded, but the underlying quality-control mechanisms remain poorly defined. Here, we identify LENG8 as a conserved RNA nuclear retention and degradation factor. LENG8 is recruited to pre-mRNAs by splicing factors, including the U1 small nuclear ribonucleoprotein particle (snRNP). It associates with PCID2 and SEM1 to form the REX (repressor of export) complex, which is conserved from yeast to humans, and causes RNA nuclear retention by acting as a dominant-negative factor for the essential mRNA export factor TREX (transcription-export)-2. Loss of LENG8 results in cytoplasmic leakage of misprocessed mRNAs, including intronically polyadenylated and intron-retained mRNAs, as well as noncoding RNAs. Moreover, LENG8 promotes nuclear RNA degradation through interactions with the RNA exosome adaptor PAXT. Together, these findings uncover a conserved RNA quality-control mechanism that ensures only correctly processed RNAs are exported.