Iwr1 Directs RNA Polymerase II Nuclear Import

SummaryRNA polymerase (Pol) II transcribes protein-coding genes in the nucleus of eukaryotic cells and consists of 12 polypeptide subunits. It is unknown how Pol II is imported into the nucleus. Here we show that Pol II nuclear import requires the protein Iwr1 and provide evidence for cyclic Iwr1 function. Iwr1 binds Pol II in the active center cleft between the two largest subunits, maybe facilitating or sensing complete Pol II assembly in the cytoplasm. Iwr1 then uses an N-terminal bipartite nuclear localization signal that is recognized by karyopherin α to direct Pol II nuclear import. In the nucleus, Iwr1 is displaced from Pol II by transcription initiation factors and nucleic acids, enabling its export and recycling. Iwr1 function is Pol II specific, transcription independent, and apparently conserved from yeast to human.

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► Iwr1 directs Pol II nuclear import via a cyclic mechanism
► Iwr1 binds karyopherin α with an N-terminal bipartite NLS
► Iwr1 binds Pol II in the active center cleft and may act as an assembly sensor
► Iwr1 function is specific for Pol II and transcription independent