Dynamics in Fip1 regulate eukaryotic mRNA 3 end processing

Ananthanarayanan Kumar, Conny W. H. Yu, Juan B. Rodríguez-Molina, Xiao Han Li, Stefan M. V. Freund (Lead / Corresponding author), Lori A. Passmore (Lead / Corresponding author)

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)
2 Downloads (Pure)


Cleavage and polyadenylation factor (CPF/CPSF) is a multiprotein complex essential for mRNA 3 end processing in eukaryotes. It contains an endonuclease that cleaves pre-mRNAs, and a polymerase that adds a poly(A) tail onto the cleaved 3 end. Several CPF subunits, including Fip1, contain intrinsically disordered regions (IDRs). IDRs within multiprotein complexes can be flexible, or can become ordered upon interaction with binding partners. Here, we show that yeast Fip1 anchors the poly(A) polymerase Pap1 onto CPF via an interaction with zinc finger 4 of another CPF subunit, Yth1. We also reconstitute a fully recombinant 850-kDa CPF. By incorporating selectively labeled Fip1 into recombinant CPF, we could study the dynamics of Fip1 within the megadalton complex using nuclear magnetic resonance (NMR) spectroscopy. This reveals that a Fip1 IDR that connects the Yth1- and Pap1-binding sites remains highly dynamic within CPF. Together, our data suggest that Fip1 dynamics within the 3 end processing machinery are required to coordinate cleavage and polyadenylation.

Original languageEnglish
Pages (from-to)1510-1526
Number of pages17
JournalGenes and Development
Issue number21-22
Early online date30 Sept 2021
Publication statusPublished - 1 Nov 2021


  • CPF
  • CPSF
  • Dynamics
  • mRNA processing
  • Polyadenylation]
  • RNA-binding protein

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology


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