Recognition of RNA polymerase II carboxy-terminal domain by 3′-RNA-processing factors

By Anton Meinhart, Patrick Cramer. 2004

343 citations recorded by the source corpus.

During transcription, RNA polymerase (Pol) II synthesizes eukaryotic messenger RNA. Transcription is coupled to RNA processing by the carboxy-terminal domain (CTD) of Pol II, which consists of up to 52 repeats of the sequence Tyr 1-Ser 2-Pro 3-Thr 4-Ser 5-Pro 6-Ser 7 (refs 1, 2). 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. Here we describe the structure of a Ser 2-phosphorylated CTD peptide bound to the CID domain of Pcf11. The CTD motif Ser 2-Pro 3-Thr 4-Ser 5 forms a β-turn that binds to a conserved groove in the CID domain. The Ser 2 phosphate group does not make direct contact with the CID domain, but may be recognized indirectly because it stabilizes the β-turn with an additional hydrogen bond. Iteration of the peptide structure results in a compact β-spiral model of the CTD. The model suggests that, during the mRNA transcription-processing cycle, compact spiral regions in the CTD are unravelled and regenerated in a phosphorylation-dependent manner.

Subfields: Molecular Biology

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Citations in the corpus

Structural insights into the recruitment of SMRT by the corepressor SHARP under phosphorylative regulation. (2013, background): “Apart from the SPOC domain, there are several domains known to act as phosphorylated Ser binding modules, such as MSH2, WD40, WW, BRCT, and CID domains, and 14-3-3 proteins (Glover et al., 2004; Hao et al., 2007; Kubicek et al., 2012; Meinhart and Cramer, 2004; Yaffe and Smerdon, 2001).”
The RNA polymerase II CTD coordinates transcription and RNA processing. (2012, background): “Pcf11, which contains an N-terminal CTD interaction domain (CID) characteristic of several CTDbinding proteins (for review, see Corden and Patturajan 1997), binds the CTD in a manner enhanced by Ser2 phosphorylation (Barilla et al. 2001; Licatalosi et al. 2002; Meinhart and Cramer 2004).”
Phosphorylation and functions of the RNA polymerase II CTD. (2006, background): “Meinhart and Cramer (2004) solved the crystal structure of the Pcf11 CID by itself, and then they soaked in a 12-residue repeat peptide in which the central Ser2 was phosphorylated.”
Progression through the RNA polymerase II CTD cycle (2009, background): “Pcf11 is an essential polyadenylation factor that preferentially binds the Ser2P CTD, where it may help to tether the polyA machinery to elongating RNApII so that it can scan for emergence of the appropriate RNA sequences (Licatalosi et al., 2002; Meinhart and Cramer, 2004).”
Ending the message: poly(A) signals then and now. (2011, background): “This factor has a CTD-interacting domain (CID) with a preference for CTD Ser 2 phosphorylation, a feature of elongating Pol II (Licatalosi et al. 2002; Meinhart and Cramer 2004).”
Elongation by RNA polymerase II: the short and long of it. (2004, background): “8; Meinhart and Cramer 2004).”
Structural insights to how mammalian capping enzyme reads the CTD code (2011, unknown): “…2B), (2) the peptidyl-proline isomerase Pin1-CTD (Verdecia et al., 2000), (3) the CTD-interacting domains (CIDs) of the 30 processing/termination factor Pcf11 and the splicing factor SCAF8 (Becker et al., 2008; Meinhart and Cramer, 2004), and (4) the small CTD phosphatase Scp1 (Zhang et al., 2006).”