LIG_Mtr4_Trf4_1

RNA processing and surveillance is a mechanisms closely regulated. In general, RNAs are degraded when their function and use is completed, which means the lifetime of a RNA molecule depends on its type (e.g. long life time for rRNA; short for aberrant RNA). There are several possible pathways for the decay of RNA substrates; one of the major players for degradation and trimming in the nucleus is the exosome (Houseley,2009). Several cofactors (such as the TRAMP complex) are needed by the exosome for target recognition. The TRAMP complex consists of a RNA helicase (MTR4), a poly(A)polymerase (Trf4 or Trf5) and a RNA-binding zinc knuckle protein (Air1 or Air2). While Air1 or Air2 recognizes the RNA substrates, Mtr4 is responsible for unwinding the RNA in order for Trf4 or Trf5 to polyadenylate the substrate (LaCava,2005). This poly(A) tail can be recognized by the exosome, initiating the degradation of the substrate (Hamill,2010). The broad spectrum of possible RNA substrates for TRAMP consists of hypomodified or incorrectly folded tRNA, rRNA, snRNA and snoRNA, incorrectly folded or spliced pre-mRNA, cryptic unstable transcripts (CUTs) and defective pre-ribosomes (Wlotzka,2011, Kadaba,2004, Carneiro,2007, Houseley,2009). Interestingly, the polyadenylation of stable mRNA by the canonical poly(A) polymerase PAP1 does not lead to degradation. The two pathways of modification therefore must be distinguishable. The length of the tail seems to be one way of encoding the addressed pathway. While the polyadenylation added by Trf4/5 is in a range of 10-50 nucleotides, PAP1 adds tails of 60-80 nucleotides (reviewed in Schmidt,2013). Furthermore, Mtr4 can modulate the activity of Trf4/5 in the TRAMP complex, resulting in a poly(A) tail length of only 3-5 nucleotides (Jia,2011).
The duplication of the polymerase Trf and the zinc knuckle protein Air arose due to a whole genome duplication event in Saccharomyces cerevisiae (15004568). The non-covalent binding of Trf4 (P53632) and the DExH-helicase core of Mtr4 (P47047, PF00270) is mediated by the described motif, which is conserved in both Trf4 (P53632) and Trf5 (P48561) in Fungi. In Vertebrata, the motif for interaction between Mtr4 and PAPD5 (human homolog of Trf5 (Houseley,2009)) slightly changed. Interestingly, the motif occurs only on human PAPD5 but not on human PAPD7 or POLS (human homolog of Trf4 Houseley,2009). The potential motif in Vertebrata (proposed through multiple sequence alignment in Losh,2015 and investigated by curator based on alignments) is described in the entry (LIG_MTR4_TRF4_2). However, note that there is no experimental evidence for this motif in Vertebrata yet.