High impact information on NRD1

• Here we show that read-through transcription from yeast small nucleolar RNA and small nuclear RNA genes into adjacent genes is prevented by a cis-acting element that is recognized, in part, by the essential RNA-binding protein Nrd1 [1].
• In this paper, we show that Nrd1 and Nab3 are required for transcription termination of CUTs [2].
• We further show that NRD1 autoregulation involves components of the exosome and a newly discovered exosome-activating complex [3].
• Nrd1 and Nab3 colocalize to regions of the genome expressing antisense CUTs, and these transcripts require yeast nuclear exosome and TRAMP components for degradation [2].
• 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 [4].

Biological context of NRD1

• Mutation of Nrd1 and Nab3 binding sites within the NRD1 mRNA leads to a relative increase in Pol II occupancy of downstream sequences [3].
• Disruption of the NRD1 gene is lethal, yet C-terminal truncations that delete the RNA recognition motif and abrogate the negative effect of the cis element nevertheless support cell growth [5].
• Nrd1 mutations share some phenotypes with exosome mutants, including increased readthrough transcription from several mRNA and sn/snoRNA genes [4].
• Nrd1 stimulates the RNA degradation activity of the exosome in vitro [4].
• Our results suggest an important role for the Nrd1p-Nab3p pathway in the control of gene expression throughout the genome [6].

Associations of NRD1 with chemical compounds

• Nrd1 has hallmarks of a heterogeneous nuclear ribonucleoprotein, including an RNA recognition motif, a region rich in RE and RS dipeptides, and a proline- and glutamine-rich domain [5].

Physical interactions of NRD1

• Saccharomyces cerevisiae Rpb7 also interacted with Nrd1, indicating that the interaction is conserved in evolution [7].

Regulatory relationships of NRD1

• In this paper, we show that NRD1 expression is regulated by Nrd1- and Nab3-directed premature termination [3].

Other interactions of NRD1

• 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 [4].
• The Paf1 complex associates with and facilitates Nrd1 recruitment to the SNR47 gene, suggesting a direct involvement in 3' end formation [8].
• We also provide evidence that Pti1p probably acts by uncoupling cleavage and polyadenylation, and functions in coordination with the Nrd1p-dependent pathway for 3' end formation of non-polyadenylated transcripts [9].
• After phosphorylation, the CTD binds tightly to a conserved CTD-interacting domain (CID) present in the proteins Pcf11 and Nrd1, which are essential and evolutionarily conserved factors for polyadenylation-dependent and -independent 3'-RNA processing, respectively [10].
• This indicates why Nrd1 cross-links near 5' ends of genes and why the Nrd1-Nab3-Sen1 termination pathway acts specifically at short Pol II-transcribed genes [11].

Analytical, diagnostic and therapeutic context of NRD1

• Chromatin immunoprecipitation and transcription run-on experiments show that, in wild-type cells, Pol II occupancy is high at the 5' end of the NRD1 gene and decreases at the 3' end [3].
• Dissection of a CUT terminator reveals a minimal element sufficient for Nrd1- and Nab3-directed termination [2].
• Previous studies have shown that Nrd1p associates with the CTD of pol II in yeast two-hybrid assays via its CTD-interaction domain (CID) [12].
• The first motif corresponds to the known Nrd1-binding site, which we have verified here by gel mobility shift assays [13].

References