A new function of ROD1 in nonsense-mediated mRNA decay

RNA-binding proteins play a crucial role in the post-transcriptional regulation of gene expression. Polypyrimidine tract binding protein (PTB in humans) has been extensively characterized as an important splicing factor, and has additional functions in 30 end processing and translation. ROD1 is a PTB paralog containing four RRM (RNA recognition motif) domains. Here, we discover a function of ROD1 in nonsense-mediated mRNA decay (NMD). We show that ROD1 and the core NMD factor UPF1 interact and co-regulate an extensive number of target genes. Using a reporter system, we demonstrate that ROD1, similarly to UPF1 and UPF2, is required for the destabilization of a known NMD substrate. Finally, we show through RIP-seq that ROD1 and UPF1 associate with a significant number of common transcripts. Structured summary of protein interactions: ROD1 physically interacts with TMED10, RNP1, PCD6, LOC493753, RBM39, BCL7C, GST-PI, AP-3, RAE1, ASH2L2, SF3B10, SDP3, CDC23, ARL10C, CAF1B, CEP55, EXPORTIN 1, NCOR1, LENG1, SNAP29, RCBTB1, RPS10, NUP155, DYNLL2, LSF, HSPC137, TNRC6C, XPO5, TMPO, SRP19, SRI, UPF2, TRF2, SSRP1, HOXB9, C11ORF73, TAF15, WDR48, SMARCA5, CUL-2, THOC2, SEC16A, CAD, LSM2, U11/U12 snRNP, TUBA, NEZHA, TRANSPORTIN 2, CGI-135, RER1, snRP E, PRPF19, TRANSPORTIN, IER3ip1, DGCR14, RPS19BP1, TOPBP1, YIP1, CPSF6, ASF1, RBM9, ARCN1, U4/U6 snRNP, CUGbp2, WDR41, p53, DNAJC9, DAZap1, TDP43, MYL6, HEY1, RAB8B, BET1, COFILIN1, MYO12A, VAT1, PRA1, MAP7D2, MAZ, PCD7, DNAJ, GNL3L, BCAS2, NUP50, RGSip1, TRIM33B, HMG-1, RAB10, ANNEXIN A2, YKT6, TRANSFERRIN, TIM44, CTP synthase, CDC42, PPIL1, HOXA9B, GCN1, hnRNP A1, LDH-B, TRAP25, mtSSB, MED8, TIA1, HMMR, B99, H1d, IMPORTIN 5, HOX7, ZMAT5, RPR1A, MARCKS, NACA, PRMT1, HOXC9, KIAA1741, HSP90AA1, LSM14, COL1A1, PRC1, CDK2, TRX-1, CSE1, COX5B, ARL1, SEPT9, BCR/ABL, CLIP-ap1, ALY, BACH1, TRIP230, DES, GFAP, APC10, MARK2, FIP1l1, RPL38, HOXC8, GATAd2A, HSPC128, TUBB, RPL11, FAM83D, UPF1, ZFP768, RPL35A, RPL30, RAB1A, BTEbp4, RNA Pol II, SEC24B, RAN, RAC3, RPS28, RPS27, snRP A, SNF5/INI1, C1ORF35, RPS7, RPS4X, RAMA1, RPS14, TUBA6, FAM128B, T-PLASTIN, FLYWCH, MYH10, ARP1, U2AF, SERPINE1, NEFM, KIAA1826, Ki-67 and RPS11 by anti bait coimmunoprecipitation (View interaction) ROD1 physically interacts with LOC100288473, PTBP1, LOC100291593, RRP36, PCMT1, BBS9, FAM83H, ARHGEF17, VIPAR, LOC100132738, PTBP2, SACS, KBTBD5, GPR98, hnRNP F, OTUD4, CAMSAP1L1, C16ORF48, FAM64A, SCN3A, IQGAP3, ZMAT5, TEX15, NOL8, RBM4, snRNP48, TMEM33, UNC45A, OGT, DIAPH3, CDK17, LARS, FAM83D, TMTC2, HSPA1A, PCM1, CSNK1A1, PHF5A, CCDC77, PLECTIN, SETX, HSPB1, HuR, NARF, MYH2, HSP90AA1, HLTF, GSK3b, CDC42, MAGOH, TRIM21, UPF1, RBMS1, ERI1, CROCC, CSNK1D, CTNNA1, AIMP2, VPS33B, FLII, CTNNB1, eIF4G2, APC, TCF20, CYCLIN T1, HIRA, BACH1, XRCC6, HMMR, RPL9, HSD17B4, MAP2, hnRNP H1, GRIA4, FRG1, HistH1e, MSH6, CELF2, CELF1, MYBbp1A, CLASP2, STIP1, GIPC1, SF3a1, CSNK1E, CDC14A, PPIH, RBM14, DYNLL2, RALY, PUF60, TRIM33, SF3b1, TARDBP, PAPD7, SF3b2, LRRFIP2, SUPT16H, FAM110B, hnRNP Ul1, KIAA1543, AXIN1, RNP1, HERC1, BANF1, XRCC5, XPC, FYTTD1, PDCD7, TAF15, YWHAH, RB1CC1, MATR3, SRRM1, SFRS14, LAGE3, XIRP1, ARHGEF2, PRPF3, PUM1 and IQCB1 by anti bait coimmunoprecipitation (View interaction) (C) 2012 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.