Structural basis for mutually exclusive co-transcriptional nuclear cap-binding complexes with either NELF-E or ARS2

Nature Communications
Wiebke M Schulze, Stephen Cusack

Abstract

Pol II transcribes diverse classes of RNAs that need to be directed into the appropriate nuclear maturation pathway. All nascent Pol II transcripts are 5'-capped and the cap is immediately sequestered by the nuclear cap-binding complex (CBC). Mutually exclusive interactions of CBC with different partner proteins have been implicated in transcript fate determination. Here, we characterise the direct interactions between CBC and NELF-E, a subunit of the negative elongation factor complex, ARS2 and PHAX. Our biochemical and crystal structure results show that the homologous C-terminal peptides of NELF-E and ARS2 bind identically to CBC and in each case the affinity is enhanced when CBC is bound to a cap analogue. Furthermore, whereas PHAX forms a complex with CBC and ARS2, NELF-E binding to CBC is incompatible with PHAX binding. We thus define two mutually exclusive complexes CBC-NELF-E and CBC-ARS2-PHAX, which likely act in respectively earlier and later phases of transcription.

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Citations

May 29, 2020·Nucleic Acids Research·Mireille MelkoTorben Heick Jensen
Sep 23, 2020·Nucleic Acids Research·Yuhui DouTorben Heick Jensen
Jan 24, 2020·Development·Yang YuEric C Lai
Apr 29, 2018·Nature Communications·Wiebke Manuela SchulzeStephen Cusack
Sep 3, 2020·Genes & Development·Xavier Rambout, Lynne E Maquat
Nov 13, 2019·Wiley Interdisciplinary Reviews. RNA·William Garland, Torben Heick Jensen
Sep 14, 2019·Theriogenology·Marzena Mogielnicka-BrzozowskaWładysław Kordan
Mar 1, 2021·Journal of Molecular Biology·Roberta Dollinger, David S Gilmour
Mar 11, 2020·Molecular Cell·Yuki AoiAli Shilatifard
Jun 2, 2021·Biochemical Society Transactions·Søren Lykke-AndersenTorben Heick Jensen
Mar 27, 2021·Annual Review of Biochemistry·Tim KrischunsStephen Cusack

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Methods Mentioned

BETA
dissection
gel
isothermal titration calorimetry
gel filtration
pull down

Software Mentioned

xProphet
REFMAC5
CCP4i
PISA
MicroCal ITC Origin
PHASER
xQuest
XDS

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