Nrd1 Interacts with the Nuclear Exosome for 3′ Processing of RNA Polymerase II Transcripts

Abstract

The exosome complex is involved in multiple RNA processing and degradation pathways. How exosome is recruited to particular RNA substrates and then chooses between RNA processing and degradation modes remains unclear. We find that the RNA binding protein Nrd1, complexed with its partners Nab3, Sen1, and cap binding complex, physically interacts with the nuclear form of exosome. Nrd1 stimulates the RNA degradation activity of the exosome in vitro. However, Nrd1 can also block 3' to 5' degradation by the exosome at some Nrd1 binding sites. Nrd1 mutations share some phenotypes with exosome mutants, including increased readthrough transcription from several mRNA and sn/snoRNA genes. Therefore, Nrd1 may recruit exosome to RNA and influence the choice between processing and degradation. Since Nrd1 is known to bind RNA polymerase II and be important for sn/snoRNA 3' end processing, Nrd1 may link transcription and RNA 3' end formation with surveillance by the exosome.

Transcription termination by nuclear RNA polymerases

“…Nrd1 (nuclear pre-mRNA down-regulation) is an essential nuclear RNA-binding protein that directs termination of snoRNA and some mRNA transcripts, in association with an interacting protein, the helicase Sen1 (Steinmetz and Brow 1996;Steinmetz et al 2001;Ursic et al 2004;Vasiljeva and Buratowski 2006). Nrd1 contains a CID (Meinhart and Cramer 2004;Meinhart et al 2005) that interacts with CTD phosphorylated at Ser5 (Conrad et al 2000;Gudipati et al 2008;Vasiljeva et al 2008a).…”

“…Nrd1 can also recruit the exosome complex, coupling the Nrd1 termination pathway to exosome-dependent trimming or degradation of transcripts ( Fig. 2; Vasiljeva and Buratowski 2006).…”

Evolution, biogenesis and function of promoter-associated RNAs

“…It has recently been shown that the RNA-binding proteins Nrd1 and Nab3 interact with the nuclear exosome and are required for the termination of RNAPII and cryptic unstable transcripts in yeast. [18][19][20] The wide variety of PAR types may in part reflect the diversity of cleavage, elongation, termination, and exosome components that form and interact with the RNAPII complex. Indeed, one of the most appealing aspects of a model of RNAPII-dependent small RNA biogenesis is that it Cell Cycle 2009; Vol.…”

The PNPase, exosome and RNA helicases as the building components of evolutionarily-conserved RNA degradation machines

“…(41/42-like heterodimer) [31] Cofactors for the exosomes without 3¢ exoRNase activity RhlB RNA helicase [50] Degradosome complex in certain bacteria [51] Ski7p and Ski RNA helicase complex [52,53] Mtr4p RNA helicase and TRAMP complex [54], Rrp47 [48], Nrd1 [55] RNA helicase associated with AU-rich element or RHAU [56], KSRP [57], TTP [58] a It is not known yet whether human nuclear and cytoplasmic exosomes contain different components.…”