Mechanisms of nuclear mRNA quality control

Quality control of spliced mRNAs requires the shuttling SR proteins Gbp2 and Hrb1

“…4b), uncovering a physical contact point of Gbp2 and Hrb1 with the NPC quality control factor Mlp1. Degradation of mRNAs that fail quality control involves the nuclear Rrp6-containing exosome 2,5 . We investigated a potential interaction between Rrp6 and Gbp2 or Hrb1 by co-IP studies and found a clear RNase sensitive physical interaction between Gbp2 or Hrb1 and Rrp6 (Fig.…”

“…In addition to its role in RNA quality control the TRAMP complex was suggested to degrade intron sequences and it was recently shown that it influences splicing 11,12 . How mRNAs are recognized as incorrect is still unclear, however, the nuclear pore complex (NPC) proteins Mlp1, Mlp2, Nup60 and Pml39 as well as the nuclear envelope protein Esc1 and the pre-mRNA retention and splicing complex protein Pml1 may play a role as their absence or mutations in their genes lead to the leakage of unspliced mRNAs into the cytoplasm 2,5 . Another exosome adapter was identified in mammalian cells and termed the nuclear exosome targeting (NEXT) complex, which is required for the degradation of noncoding transcripts 13 .…”

“…Results of failure on a single cellular level could be adecreased viability or in multicellular organisms diseases like cancer or neurodegenerative diseases 1 . At all levels of nuclear mRNA maturation, during transcription, splicing or 3 0 -end processing defective mRNAs can be produced, but are then caught and eliminated by the nuclear surveillance machinery [2][3][4][5] . Although only little is known about the underlying mechanisms, degradation of faulty mRNAs requires the nuclear exosome that contains a specific nuclear ribonuclease Rrp6 in addition to a nine-subunit exosome core associated with the 3 0 -5 0 exoribonuclease Dis3/Rrp44 (refs 6-8).…”

Crossing the borders: Poly(A)-binding proteins working on both sides of the fence

“…Similar to capping, splicing and 3' end processing, several mRNA export factors are recruited during transcription to allow efficient nucleo-cytoplasmic transport of mRNAs. 6,17 Biochemical evidence indicates that transit of the mRNP through the NPC involves remodelling of several proteins present on the mRNA; 18,19 yet, the extent of mRNP remodelling is poorly understood and remains an active area of research. According to the steady state distribution of PABPN1 and PABPC1 to the nucleus and the cytoplasm, respectively, it has been proposed that PABPC1 substitutes for PABPN1 after nuclear export of the mRNA.…”

“…1 The recruited complexes are subsequently transferred onto nascent transcripts for the addition of a 5' cap structure, the removal of introns by the spliceosome, and the addition of a 3' poly(A) tail. [2][3][4] Studies during the past decade have shed light on evolutionarily conserved quality control systems that monitor the accuracy of these maturation events before an mRNA is exported through the nuclear pore complex, [5][6][7][8] thereby improving the fidelity of gene expression. Interestingly, evidence now converge toward the nature of the poly(A) tail as a critical mean of discriminating between normal and aberrant mRNAs.…”