Distinct Mechanisms of Transcription Initiation by RNA Polymerases I and II

Abstract

RNA polymerases I and II (Pol I and Pol II) are the eukaryotic enzymes that catalyze DNA-dependent synthesis of ribosomal RNA and messenger RNA, respectively. Recent work shows that the transcribing forms of both enzymes are similar and the fundamental mechanisms of RNA chain elongation are conserved. However, the mechanisms of transcription initiation and its regulation differ between Pol I and Pol II. Recent structural studies of Pol I complexes with transcription initiation factors provided insights into how the polymerase recognizes its specific promoter DNA, how it may open DNA, and how initiation may be regulated. Comparison with the well-studied Pol II initiation system reveals a distinct architecture of the initiation complex and visualizes promoter- and gene-class-specific aspects of transcription initiation. On the basis of new structural studies, we derive a model of the Pol I transcription cycle and provide a molecular movie of Pol I transcription that can be used for teaching.

Genome-wide analyses of chromatin interactions after the loss of Pol I, Pol II and Pol III

“…RNA polymerases synthesize RNA, forming DNA, RNA, and protein ternary complexes in the nucleus [27][28][29]. Pol I, Pol II, and Pol III are three distinct DNAdependent RNA polymerases that function together with thousands of transcriptional and chromatin regulators to synthesize rRNA, mRNA, and tRNA, respectively [9,[30][31][32][33][34][35][36]. Although the structure and function of RNA polymerases have been studied for 50 years [37], in particular, the roles of Pol I and Pol III in 3D chromatin organizations are poorly investigated.…”

Effective targeting of RNA polymerase I in treatment‐resistant prostate cancer

“…rRNA transcription constitutes 60% of total cellular transcription and is a highly regulated multistep process . Briefly, rRNA transcription initiation occurs upon the assembly of multisubunit preinitiation complex including SL1 and RRN3 that binds the rDNA promoter and facilitates the loading of the 13‐subunit Pol I complex . Pol I transcribes a long polycistronic 47S rRNA precursor.…”

“…8 Briefly, rRNA transcription initiation occurs upon the assembly of multisubunit preinitiation complex including SL1 and RRN3 that binds the rDNA promoter and facilitates the loading of the 13-subunit Pol I complex. 9,10 Pol I transcribes a long polycistronic 47S rRNA precursor. The 47S rRNA contains 5ʹ and 3ʹ external transcribed spacers (ETS) and internal transcribed spacers that are rapidly cleaved to yield mature 28S, 18S, and 5.8S rRNAs, which are assembled into the large and small subunit ribosomes through multiple maturation and processing steps.…”

RNA polymerase I passage through nucleosomes depends on its lobe binding subunits

“…Eukaryotic RNA polymerases (RNAPs) share many structural and functional features, but are also are highly specialized transcription machineries. The molecular nature of their specialisation is presently subject of intensive investigations (see as reviews [1][2][3]. In most eukaryotes, RNA polymerase I (Pol I) transcribes only one gene locus, the multi copy ribosomal (r)RNA genes.…”

“…Whether the Pol I counterparts play a role in nucleosomal transcription remains to be elucidated. The heterodimer Rpa34.5/Rpa49 of Pol I corresponds to Rpc37/Rpc53 of Pol III [3] and associates together with the N-terminal part of Rpa12.2 to the Pol I lobe structure, thereby forming a lobe binding module (hereafter called lb-module). The heterodimer Rpa34.5/Rpa49 consists of three subdomains: a dimerization module formed by Rpa34.5 and the N-terminal part of Rpa49 (full length Rpa34.5 and aa 1-110 of Rpa49), the A49 linker (aa 105-187 of Rpa49), and the C-terminal part of Rpa49 (aa 187-415, hereafter called Rpa49CT).…”