title: Nup358 binds to AGO proteins through its SUMO-interacting motifs and promotes the association of target mRNA with miRISC.
abstract: MicroRNA (miRNA)-guided mRNA repression, mediated by the miRNA-induced silencing complex (miRISC), is an important component of post-transcriptional gene silencing. However, how miRISC identifies the target mRNA in vivo is not well understood. Here, we show that the nucleoporin Nup358 plays an important role in this process. Nup358 localizes to the nuclear pore complex and to the cytoplasmic annulate lamellae (AL), and these structures dynamically associate with two mRNP granules: processing bodies (P bodies) and stress granules (SGs). Nup358 depletion disrupts P bodies and concomitantly impairs the miRNA pathway. Furthermore, Nup358 interacts with AGO and GW182 proteins and promotes the association of target mRNA with miRISC A well-characterized SUMO-interacting motif (SIM) in Nup358 is sufficient for Nup358 to directly bind to AGO proteins. Moreover, AGO and PIWI proteins interact with SIMs derived from other SUMO-binding proteins. Our study indicates that Nup358-AGO interaction is important for miRNA-mediated gene silencing and identifies SIM as a new interacting motif for the AGO family of proteins. The findings also support a model wherein the coupling of miRISC with the target mRNA could occur at AL, specialized domains within the ER, and at the nuclear envelope.
authors.affiliation: National Centre for Cell Science, S.P. Pune University Campus, Pune, India.
authors.forename: Manas Ranjan
authors.initials: MR
authors.lastname: Sahoo
authors.affiliation: National Centre for Cell Science, S.P. Pune University Campus, Pune, India.
authors.forename: Swati
authors.initials: S
authors.lastname: Gaikwad
authors.affiliation: National Centre for Cell Science, S.P. Pune University Campus, Pune, India.
authors.forename: Deepak
authors.initials: D
authors.lastname: Khuperkar
authors.affiliation: National Centre for Cell Science, S.P. Pune University Campus, Pune, India.
authors.forename: Maitreyi
authors.initials: M
authors.lastname: Ashok
authors.affiliation: National Centre for Cell Science, S.P. Pune University Campus, Pune, India.
authors.forename: Mary
authors.initials: M
authors.lastname: Helen
authors.affiliation: National Centre for Cell Science, S.P. Pune University Campus, Pune, India.
authors.forename: Santosh Kumar
authors.initials: SK
authors.lastname: Yadav
authors.affiliation: National Centre for Cell Science, S.P. Pune University Campus, Pune, India.
authors.forename: Aditi
authors.initials: A
authors.lastname: Singh
authors.affiliation: National Centre for Cell Science, S.P. Pune University Campus, Pune, India.
authors.forename: Indrasen
authors.initials: I
authors.lastname: Magre
authors.affiliation: National Centre for Cell Science, S.P. Pune University Campus, Pune, India.
authors.forename: Prachi
authors.initials: P
authors.lastname: Deshmukh
authors.affiliation: National Centre for Cell Science, S.P. Pune University Campus, Pune, India.
authors.forename: Supriya
authors.initials: S
authors.lastname: Dhanvijay
authors.affiliation: National Centre for Cell Science, S.P. Pune University Campus, Pune, India.
authors.forename: Pabitra Kumar
authors.initials: PK
authors.lastname: Sahoo
authors.affiliation: Division of Biology, Indian Institute of Science Education and Research, Pune, India.
authors.forename: Yogendra
authors.initials: Y
authors.lastname: Ramtirtha
authors.affiliation: Division of Biology, Indian Institute of Science Education and Research, Pune, India.
authors.forename: Mallur Srivatsan
authors.initials: MS
authors.lastname: Madhusudhan
authors.affiliation: Division of Biology, Indian Institute of Science Education and Research, Pune, India.
authors.forename: Pananghat
authors.initials: P
authors.lastname: Gayathri
authors.affiliation: National Centre for Cell Science, S.P. Pune University Campus, Pune, India.
authors.forename: Vasudevan
authors.initials: V
authors.lastname: Seshadri
authors.affiliation: National Centre for Cell Science, S.P. Pune University Campus, Pune, India josephj@nccs.res.in.
authors.forename: Jomon
authors.identifier: 0000-0002-3042-6286
authors.initials: J
authors.lastname: Joseph
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D060565:Argonaute Proteins / Q000737:chemistry / Q000378:metabolism*; D002460:Cell Line; D020868:Gene Silencing; D006801:Humans; D045586:Intranuclear Inclusion Bodies / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008954:Models, Biological; D008958:Models, Molecular; D018832:Molecular Chaperones / Q000737:chemistry / Q000378:metabolism*; D028861:Nuclear Pore Complex Proteins / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D054730:Protein Interaction Domains and Motifs; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D034743:RNA-Induced Silencing Complex / Q000378:metabolism*; D015398:Signal Transduction; D016335:Zinc Fingers
chemical_list: D060565:Argonaute Proteins; D035683:MicroRNAs; D018832:Molecular Chaperones; D028861:Nuclear Pore Complex Proteins; D012333:RNA, Messenger; D034743:RNA-Induced Silencing Complex; C094493:ran-binding protein 2
keywords: Argonaute; Nup358; annulate lamellae; miRNA; nucleoporin