Regulating the Shuttling of Eukaryotic RNA Polymerase II

Abstract

The eukaryotic RNA polymerase II (RNAPII) transcribes most protein-coding RNAs (mRNAs) and the capped noncoding RNAs (ncRNAs), including microRNAs (miRNAs), small nuclear RNAs (snRNAs), and small nucleolar RNAs (snoRNAs) (10). In the past 3 decades, our knowledge about the functional role of RNAPII during gene transcription has dramatically advanced (8). However, there are still several open questions regarding the regulatory mechanisms involved in the steps before and after transcription. In particular, how RNAPII is imported into the nucleus remains elusive. In this issue, Carre ´ and Shiekhattar (3) report that the evolutionarily conserved GTPases GPN1 and GPN3 stably associate with and regulate the nuclear import of the human RNAPII. These exciting results now make it possible to begin to dissect the regulatory pathways of the intracellular localization and nuclear import of RNAPII. Recently, the structures and subunit compositions of the three RNA polymerases (Table 1) have been characterized (4). RNAPII is a highly conserved enzyme composed of 12 subunits, 10 of which form the central core. The other two subunits (Rpb4 and Rpb7) form a peripheral heterodimer that protrudes out from the core enzyme structure. This stabilizes the RNAPII complex in clamp-closed conformation, favoring efficient transcription initiation. Rpb10 and Rpb12 are common subunits for all of the eukaryotic RNA polymerases and are implicated in the interaction with the basal transcription factors, such as the TATA box-binding protein (TBP). These interactions lead to the formation of the preinitiation complex (PIC), which contains RNAPII as well as the general transcription factors TFIIA, TFIIB, TFIID, TFIIE, TFIIF, and TFIIH. In the past years, numerous coactivators that both facilitate the access of PIC to its target promoters and increase the stability of the complex have been functionally characterized. Recent data (1) indicate that the RNAPII assembly pathway occurs in the cytoplasm and that assembly is coordinated by the consecutive actions of the cochaperone hSpagh and the chaperone Hsp90. The two largest subunits, Rpb1 and Rpb2, are initially preassembled into two separated subcomplexes, together with several other subunits that are either common to all three