A CAF40-binding motif facilitates recruitment of the CCR4-NOT complex to mRNAs targeted by Drosophila Roquin.
Human (Hs) Roquin1 and Roquin2 are RNA-binding proteins that promote mRNA target degradation through the recruitment of the CCR4-NOT deadenylase complex and are implicated in the prevention of autoimmunity. Roquin1 recruits CCR4-NOT via a C-terminal region that is not conserved in Roquin2 or in invertebrate Roquin. Here we show that Roquin2 and Drosophila melanogaster (Dm) Roquin also interact with the CCR4-NOT complex through their C-terminal regions. The C-terminal region of Dm Roquin contains multiple motifs that mediate CCR4-NOT binding. One motif binds to the CAF40 subunit of the CCR4-NOT complex. The crystal structure of the Dm Roquin CAF40-binding motif (CBM) bound to CAF40 reveals that the CBM adopts an α-helical conformation upon binding to a conserved surface of CAF40. Thus, despite the lack of sequence conservation, the C-terminal regions of Roquin proteins act as an effector domain that represses the expression of mRNA targets via recruitment of the CCR4-NOT complex.
Department of Biochemistry, Max Planck Institute for Developmental Biology, Spemannstrasse 35, Tübingen 72076, Germany.
Annamaria
A
Sgromo
Department of Biochemistry, Max Planck Institute for Developmental Biology, Spemannstrasse 35, Tübingen 72076, Germany.
Tobias
T
Raisch
Department of Biochemistry, Max Planck Institute for Developmental Biology, Spemannstrasse 35, Tübingen 72076, Germany.
Praveen
P
Bawankar
Department of Biochemistry, Max Planck Institute for Developmental Biology, Spemannstrasse 35, Tübingen 72076, Germany.
Dipankar
D
Bhandari
Department of Biochemistry, Max Planck Institute for Developmental Biology, Spemannstrasse 35, Tübingen 72076, Germany.
Ying
Y
Chen
Department of Biochemistry, Max Planck Institute for Developmental Biology, Spemannstrasse 35, Tübingen 72076, Germany.
Duygu
D
Kuzuoğlu-Öztürk
Department of Biochemistry, Max Planck Institute for Developmental Biology, Spemannstrasse 35, Tübingen 72076, Germany.
Oliver
0000-0001-5818-6248
O
Weichenrieder
Department of Biochemistry, Max Planck Institute for Developmental Biology, Spemannstrasse 35, Tübingen 72076, Germany.
Elisa
0000-0001-7365-2649
E
Izaurralde
D000818:Animals; D001665:Binding Sites; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000378:metabolism; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006801:Humans; D020871:RNA Stability / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012260:Ribonucleases / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
C528690:CNOT1 protein, human; D002352:Carrier Proteins; D029721:Drosophila Proteins; C568695:NOT1 protein, Drosophila; C000592051:RC3H1 protein, human; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D011994:Recombinant Proteins; D014157:Transcription Factors; D044767:Ubiquitin-Protein Ligases; D012260:Ribonucleases; C445084:mRNA deadenylase