Methods for modulating rna splicing

Abstract

In one aspect, described herein is a recognition element for splicing modifier (REMS) that can be recognized by a compound provided herein. In another aspect, described herein are methods for modulating the amount of a product of a gene, wherein a precursor RNA transcript transcribed from the gene contains a REMS, and the methods utilizing a compound described herein. More particularly, described herein are methods for modulating the amount of an RNA transcript or protein product encoded by a gene, wherein a precursor RNA transcript transcribed from the gene comprises a REMS, and the methods utilizing a compound described herein. In another aspect, provided herein are artificial gene constructs comprising a REMS, and uses of those artificial gene constructs to modulate functional protein production. In another aspect, provided herein are methods for altering endogenous genes to comprise a REMS, and the use of a compound described herein to modulate the functional protein produced from such altered endogenous genes.

1 .- 23 . (canceled) 
     
     
         24 . A method for modulating the amount of an RNA transcript produced from a precursor RNA of a gene, the method comprising contacting the compound, or a form thereof, with the precursor RNA in a cell, wherein the precursor RNA comprises a recognition element for splicing modifier (REMS) having the sequence GAgurngn (SEQ ID NO: 1), r is A or G, n is any nucleotide; the compound or form thereof has the structure: 
       
         
           
           
               
               
           
         
       
       and the gene that is selected from ABCA1, ABCB7, ABCC1, ABHD10, ABL2, ABLIM3, ACACA, ACADVL, ACAT2, ADAM12, ADAM15, ADAM17, ADAM33, AFF2, AGK, AGPAT3, AGPS, AHCYL2, AHCYL2, AHDC1, AHRR, AJUBA, AK021888, AK310472, AKAP1, AKAP1, ANK2, AKAP9, AKNA, ALCAM, ALDH4A1, ALDH4A1, AMPD2, ANKRD17, ANKFY1, ANKHD1-EIF4EBP3, ANKRD17, ANKS6, ANP32A, ANXA11, ANXA6, AP2B1, AP2B1, APLP2, APAF1, APLP2, APP, APPL2, APTX, ARHGAP22, ARID1A, ARID2, ARMCX6, ARMCX3, ASAP1, ASL, ASNS, ASPH, ASPH, ATAD2B, ATF7IP, ATG9A, ATMIN, ATP2C1, ATXN3, AURKA, AXIN1, AXIN1, B4GALT2, BACE1, BAG2, BASP1, BASP1, BC033281, BCAR3, BEND6, BICD1, BIN1, BNC1, BRD2, BRPF1, BSCL2, BTBD10, BZW1, C11orf30, C11orf73, C11orf73, C17orf76-AS1, C4orf27, C5orf24, C6orf48, C9orf69, CAB39, CALU, CAMKK1, CAPNS1, CASC3, CASP8AP2, CAV1, CCAR1, CCDC77, CCDC88A, CCDC88A, CCDC92, CDC25B, CCT6A, CD276, CD46, CDC25B, CDC40, CDC42BPA, CDC42BPA, CDKAL1, CDCA7, CDH11, CDH13, CDK11B, CDK16, CEP68, CFLAR, CHD8, CIZ1, CLIC1, CLIC1, COL12A1, CLK4, CNOT1, COG1, COL12A1, COL1A1, COL1A2, COL3A1, COL5A2, COL6A1, COPS7B, CPEB2, CREB5, CRLS1, CRTAP, CSDE1, CSNK1A1, CTDSP2, CTNND1, CUL2, CUL2, CUL4A, CUL4A, DAXX, CUX1, CUX1, CYB5B, CYBRD1, CYP51A1, DAB2, DACT1, DCAF10, DARS, DCAF10, DCAF11, DCBLD2, DCUN1D4, DDAH1, DDAH2, DDHD2, DDR1, DDX39B, DDX39B, DDX42, DDX42, DENND1A, DENND1B, DENND5A, DENND5A, DGKA, DGCR2, DGKA, DHCR24, DHCR7, DHFR, DHX9, DIAPH1, DIAPH3, DIAPH3, DIS3L, DKFZp434M1735, DKK3, DKK3, DLC1, DNM2, DOCK1, DPP8, DSEL, DST, DSTN, EBF1, EEA1, EEF1A1, EFCAB14, EGR1, ERGIC3, EIF4G1, EHMT2, EIF2B3, EIF4G1, EIF4G2, EIF4G3, ELF2, ENG, ENG, ENPP2, ENSA, EPN1, EPN1, EPT1, ERC1, ETV5, EXO1, FAM111A, EXTL2, EYA3, FADS1, FADS2, FAF1, FAM198B, FAM219A, FAM219B, FAM3C, FAM65A, FBXO10, FBXO18, FBXO31, FBXO34, FBXO9, FBXO9, FDFT1, FDPS, FER, FEZ1, FGD5-AS1, FGD5-AS1, FLII, FGFRL1, FHOD3, FLII, FLNB, FN1, FNBP1, FOCAD, FOS, FOSB, FOSL1, FOXK1, FOXK1, FOXM1, FOXM1, FOXM1, GABPB1, FUS, FYN, FYN, GABPB1, GABPB1, GALC, GALNT1, GAS7, GBA2, GGCT, GCFC2, GGCT, GHDC, GIGYF2, GJC1, GMIP, GNA13, GNAS, GNL3L, GOLGA2, GOLGA4, GPR1, GOLGB1, GPR89A, GORASP1, GPSM2, GREM1, GRK6, GSE1, HAUS6, GTF2H2B, HAS2, HAT1, HAUS3, HDAC7, HEG1, HLA-A, HLA-E, HLTF, HLTF, HP1BP3, HMGA1, HMGA1, HMGB1, HMGCR, HMGCS1, HMOX1, HNRNPR, HNRNPUL1, HP1BP3, HRH1, HSD17B12, HSD17B4, HTT, IARS, IDH1, IDI1, IGF2BP2, IL6ST, INHBA, INSIG1, KANSL3, IQCE, ITGAV, ITGB5, ITSN1, ITM2C, KCNK2, KIAA1033, KIAA1033, KIAA1143, KIAA1199, KIAA1522, KIAA1524, KIAA1549, KIF14, KIAA1715, KIF2A, KIF3A, KLC1, KLC2, KLF6, KLHL7, KRT18, KRT19, KRT34, KRTAP2-3, LAMA2, LAMA2, LAMA2, LARP4, LAMB1, LARP7, LATS2, LDLR, LEMD3, LGALS8, LIMS1, LIMS1, LINC00341, LINC00341, LINC00657, LINC00657, LONP1, LMAN2L, LMO7, LONP1, LOX, LRCH4, LRCH4, LRIG1, LRP8, LRRC8A, LSS, LTBR, LUC7L2, LZTS2, MADD, MAGED4, MAGED4B, MAGED4B, MAN1A2, MAN1A2, MAP4K4, MED1, MBD1, MBOAT7, MDM2, MEDAG, MEF2D, MEIS2, MEMO1, MEPCE, MFGE8, MICAL2, MINPP1, MKL1, MKLN1, MKNK2, MLST8, MLLT4, MMAB, MMS19, MMS22L, MSL3, MPPE1, MPZL1, MSANTD3, MRPL3, MSC, MSH2, MSH6, MSL3, MSMO1, MSRB3, MTAP, MTERFD1, MTHFD1L, MTMR9, MTRR, MUM1, MVD, MVK, MYADM, MYLK, MYO1D, MYO9B, MYOF, NAA35, NADK, NASP, NAV1, NAV2, NAV2, NCOA1, NCOA3, NCOA4, NCSTN, NFE2L1, NELFA, NEO1, NEURL1B, NF2, NFE2L1, NID1, NFX1, NID1, NID2, NIPA1, NKX3-1, NOL10, NPEPPS, NOMO3, NPEPPS, NRD1, NREP, NRG1, NSUN4, NT5C2, NT5E, NTNG1, NUDT4, NUP153, NUP35, NUP50, NUPL1, NUSAP1, NUSAP1, ODF2, OS9, OSBPL6, OSMR, P4HA1, P4HA1, P4HB, PABPC1, PAK4, PAPD4, PAPD4, PAPD4, PCBP2, PARD3, PARN, PARP1, PARP14, PARP4, PARVB, PCBP2, PCBP4, PCBP4, PCDHGB3, PCGF3, PCGF3, PDLIM7, PCM1, PCMTD2, PCNXL2, PCSK9, PDE4A, PDE7A, PDXDC1, PEPD, PEX5, PFKP, PHF19, PHF8, PHRF1, PHRF1, PHTF2, PHTF2, PI4K2A, PIEZO1, PIGU, PIK3C2B, PITPNA, PITPNB, PITPNM1, PLAU, PLAU, PLEKHB2, PLEC, PMS1, PLSCR3, PLXNB2, PLXNC1, PMS1, POU2F1, POLE3, POLR3D, POSTN, POU2F1, PPAPDC1A, PPARA, PPARA, PPP6R1, PPHLN1, PPIP5K1, PPP1R12A, PPP6R2, PRKACB, PRKDC, PRMT1, PRNP, PRSS23, PSMA4, PTK2B, PSMC1, PSMD6, PTPN14, PTPN14, PUF60, PUS7, PVR, PXN, QKI, RAB23, RAB23, RAD23B, RAB2B, RAB34, RAD1, RAD23B, RALB, RAP1A, RAP1GDS1, RARG, RASSF8, RASSF8, RBCK1, RBCK1, RBFOX2, RBFOX2, RBM10, RCC1, RFTN1, RNF19A, RFWD2, RGS10, RGS3, RIF1, RNF14, RNF19A, RNF38, RNFT1, RPL10, RPS6KC1, RRBP1, RWDD4, RWDD4, SAR1A, SAMD9, SAMD9L, SART3, SCAF4, SCAF4, SCAF8, SCD, SCLT1, SCO1, SDCBP, SEC14L1, SEC22A, SEC24B, SEC61A1, SEPT9, SERPINE2, SF1, SF1, SH3RF1, SGOL2, SLC25A17, SKIL, SLC25A17, SLC39A3, SLC41A1, SLC4A4, SLC7A6, SLC7A8, SMARCA4, SMARCC2, SMC4, SMC6, SMCHD1, SMG1, SMYD3, SMPD4, SMYD3, SMYD5, SNAP23, SNHG16, SNX14, SOCS2, SON, SOS2, SPATA20, SPATS2, SPG20, SPRED2, STAU1, SQLE, SQRDL, SQSTM1, SRCAP, SREBF1, SREBF1, SREK1, SREBF1, STARD4, SRSF3, STAT1, STAT3, STAU1, STC2, STEAP2, STEAP2, STRIP1, STRN3, STX16, SUPT20H, SYNE1, SYNE2, SYNE2, SYT15, SYTL2, TACC1, TAF2, TANC2, TARBP1, TARBP1, TBC1D15, TARS, TBL2, TCF7L2, TENC1, TENM2, TEP1, TET3, TGFBR1, TFCP2, TGFBI, TGFBR1, TGFBRAP1, THADA, THAP4, THRB, TIMP2, TJP2, TLE3, TLK1, TMEM154, TMEM47, TMEM47, TNKS1BP1, TMEM63A, TNC, TNFAIP3, TNFRSF12A, TNS1, TNIP1, TNPO3, TNS1, TNS3, TOE1, TOMM40, TOMM5, TOMM5, TRAF3, TOPORS, TP53INP1, TRAF3, TRAK1, TRAPPC12, TRIB1, TRIM2, TRIM23, TRIM26, TRIM28, TRIM65, TRIM65, TRMT1L, TRIM65, TSC2, TRPS1, TSC2, TSHZ1, TSPAN2, TTC7A, TUBB2C, TUBB3, TXNL1, TXNRD1, TXNRD1, UBE2G2, U2SURP, UBAP2L, UBAP2L, UBE2V1, UBE2G2, UBE2V1, UBQLN4, UCHL5, UHMK1, UHRF1BP1L, UNC5B, USP19, USP7, VANGL1, VANGL1, VIPAS39, VARS2, VCL, VPS13A, VPS29, VWA8, VPS51, VWA8, WDR19, WDR37, WDR48, WIPF1, WIPF1, WWTR1, WNT5B, WSB1, WSB1, XIAP, WWTR1, XRN2, YAP1, YES1, YPEL5, YPEL5, YTHDF3, Z24749, ZAK, ZBTB10, ZBTB24, ZBTB7A, ZC3H12C, ZC3H14, ZC3H18, ZCCHC11, ZEB1, ZEB2, ZFAND1, ZFAND5, ZFAND5, ZMIZ1, ZHX3, ZMIZ1, ZMYM2, ZMYM2, ZNF219, ZNF12, ZNF148, ZNF219, ZNF227, ZNF24, ZNF268, ZNF28, ZNF281, ZNF335, ZNF37A, ZNF37BP, ZNF395, ZNF583, ZNF621, ZNF652, ZNF655, ZNF674, ZNF74, ZNF764, ZNF778, ZNF780A, ZNF827, ZNF839, or ZNF91. 
     
     
         25 . The method of  claim 24 , wherein the precursor RNA sequence comprises exons, one or more introns, a 5′ splice site, a branch point, and a 3′ splice site; and wherein the 5′ splice site comprises the REMS and is upstream of the branch point and the 3′ splice site. 
     
     
         26 . The method of  claim 24 , wherein the REMS is endogenous. 
     
     
         27 . The method of  claim 24 , wherein the REMS is non-endogenous. 
     
     
         28 . The method of  claim 24 , wherein the cell is in a cell culture or cell lysate. 
     
     
         29 . The method of  claim 24 , wherein the REMS comprises the sequence ANGAguragu (SEQ ID NO: 4), wherein r is A or G and N is any nucleotide. 
     
     
         30 . The method of  claim 24 , wherein the precursor RNA results from aberrant expression of the gene. 
     
     
         31 . The method of  claim 30 , wherein aberrant expression is an abnormal down regulation of an RNA transcript in the cell relative to a corresponding healthy cell. 
     
     
         32 . The method of  claim 30 , wherein the cell is (a) from a cell line known to have aberrant RNA transcript levels for the gene or; (b) from a subject with a disease associated with an aberrant amount of an RNA transcript for the gene. 
     
     
         33 . The method of  claim 24 , wherein the gene is ABHD10, APLP2, ARMCX6, COL1A1, COL1A2, COL3A1, COL5A2, DIAPH3, ERGIC3, FADS2, FN1, FOXM1, GALC, GGCT, LAMA2, LARP7, MADD, PARP1, PRKDC, RCC1, STRN3, or VPS29. 
     
     
         34 . A method for modulating the amount of a functional protein produced from a precursor RNA of a gene, the method comprising contacting the compound, or a form thereof, with a precursor RNA in a cell, wherein the precursor RNA comprises a REMS having the sequence GAgurngn (SEQ ID NO: 1), r is A or G, n is any nucleotide; the compound or form thereof has the structure: 
       
         
           
           
               
               
           
         
       
       and the gene that is selected from ABCA1, ABCB7, ABCC1, ABHD10, ABL2, ABLIM3, ACACA, ACADVL, ACAT2, ADAM12, ADAM15, ADAM17, ADAM33, AFF2, AGK, AGPAT3, AGPS, AHCYL2, AHCYL2, AHDC1, AHRR, AJUBA, AK021888, AK310472, AKAP1, AKAP1, ANK2, AKAP9, AKNA, ALCAM, ALDH4A1, ALDH4A1, AMPD2, ANKRD17, ANKFY1, ANKHD1-EIF4EBP3, ANKRD17, ANKS6, ANP32A, ANXA11, ANXA6, AP2B1, AP2B1, APLP2, APAF1, APLP2, APP, APPL2, APTX, ARHGAP22, ARID1A, ARID2, ARMCX6, ARMCX3, ASAP1, ASL, ASNS, ASPH, ASPH, ATAD2B, ATF7IP, ATG9A, ATMIN, ATP2C1, ATXN3, AURKA, AXIN1, AXIN1, B4GALT2, BACE1, BAG2, BASP1, BASP1, BC033281, BCAR3, BEND6, BICD1, BIN1, BNC1, BRD2, BRPF1, BSCL2, BTBD10, BZW1, C11orf30, C11orf73, C11orf73, C17orf76-AS1, C4orf27, C5orf24, C6orf48, C9orf69, CAB39, CALU, CAMKK1, CAPNS1, CASC3, CASP8AP2, CAV1, CCAR1, CCDC77, CCDC88A, CCDC88A, CCDC92, CDC25B, CCT6A, CD276, CD46, CDC25B, CDC40, CDC42BPA, CDC42BPA, CDKAL1, CDCA7, CDH11, CDH13, CDK11B, CDK16, CEP68, CFLAR, CHD8, CIZ1, CLIC1, CLIC1, COL12A1, CLK4, CNOT1, COG1, COL12A1, COL1A1, COL1A2, COL3A1, COL5A2, COL6A1, COPS7B, CPEB2, CREB5, CRLS1, CRTAP, CSDE1, CSNK1A1, CTDSP2, CTNND1, CUL2, CUL2, CUL4A, CUL4A, DAXX, CUX1, CUX1, CYB5B, CYBRD1, CYP51A1, DAB2, DACT1, DCAF10, DARS, DCAF10, DCAF11, DCBLD2, DCUN1D4, DDAH1, DDAH2, DDHD2, DDR1, DDX39B, DDX39B, DDX42, DDX42, DENND1A, DENND1B, DENND5A, DENND5A, DGKA, DGCR2, DGKA, DHCR24, DHCR7, DHFR, DHX9, DIAPH1, DIAPH3, DIAPH3, DIS3L, DKFZp434M1735, DKK3, DKK3, DLC1, DNM2, DOCK1, DPP8, DSEL, DST, DSTN, EBF1, EEA1, EEF1A1, EFCAB14, EGR1, ERGIC3, EIF4G1, EHMT2, EIF2B3, EIF4G1, EIF4G2, EIF4G3, ELF2, ENG, ENG, ENPP2, ENSA, EPN1, EPN1, EPT1, ERC1, ETV5, EXO1, FAM111A, EXTL2, EYA3, FADS1, FADS2, FAF1, FAM198B, FAM219A, FAM219B, FAM3C, FAM65A, FBXO10, FBXO18, FBXO31, FBXO34, FBXO9, FBXO9, FDFT1, FDPS, FER, FEZ1, FGD5-AS1, FGD5-AS1, FLII, FGFRL1, FHOD3, FLII, FLNB, FN1, FNBP1, FOCAD, FOS, FOSB, FOSL1, FOXK1, FOXK1, FOXM1, FOXM1, FOXM1, GABPB1, FUS, FYN, FYN, GABPB1, GABPB1, GALC, GALNT1, GAS7, GBA2, GGCT, GCFC2, GGCT, GHDC, GIGYF2, GJC1, GMIP, GNA13, GNAS, GNL3L, GOLGA2, GOLGA4, GPR1, GOLGB1, GPR89A, GORASP1, GPSM2, GREM1, GRK6, GSE1, HAUS6, GTF2H2B, HAS2, HAT1, HAUS3, HDAC7, HEG1, HLA-A, HLA-E, HLTF, HLTF, HP1BP3, HMGA1, HMGA1, HMGB1, HMGCR, HMGCS1, HMOX1, HNRNPR, HNRNPUL1, HP1BP3, HRH1, HSD17B12, HSD17B4, HTT, IARS, IDH1, IDI1, IGF2BP2, IL6ST, INHBA, INSIG1, KANSL3, IQCE, ITGAV, ITGB5, ITSN1, ITM2C, KCNK2, KIAA1033, KIAA1033, KIAA1143, KIAA1199, KIAA1522, KIAA1524, KIAA1549, KIF14, KIAA1715, KIF2A, KIF3A, KLC1, KLC2, KLF6, KLHL7, KRT18, KRT19, KRT34, KRTAP2-3, LAMA2, LAMA2, LAMA2, LARP4, LAMB1, LARP7, LATS2, LDLR, LEMD3, LGALS8, LIMS1, LIMS1, LINC00341, LINC00341, LINC00657, LINC00657, LONP1, LMAN2L, LMO7, LONP1, LOX, LRCH4, LRCH4, LRIG1, LRP8, LRRC8A, LSS, LTBR, LUC7L2, LZTS2, MADD, MAGED4, MAGED4B, MAGED4B, MAN1A2, MAN1A2, MAP4K4, MED1, MBD1, MBOAT7, MDM2, MEDAG, MEF2D, MEIS2, MEMO1, MEPCE, MFGE8, MICAL2, MINPP1, MKL1, MKLN1, MKNK2, MLST8, MLLT4, MMAB, MMS19, MMS22L, MSL3, MPPE1, MPZL1, MSANTD3, MRPL3, MSC, MSH2, MSH6, MSL3, MSMO1, MSRB3, MTAP, MTERFD1, MTHFD1L, MTMR9, MTRR, MUM1, MVD, MVK, MYADM, MYLK, MYO1D, MYO9B, MYOF, NAA35, NADK, NASP, NAV1, NAV2, NAV2, NCOA1, NCOA3, NCOA4, NCSTN, NFE2L1, NELFA, NEO1, NEURL1B, NF2, NFE2L1, NID1, NFX1, NID1, NID2, NIPA1, NKX3-1, NOL10, NPEPPS, NOMO3, NPEPPS, NRD1, NREP, NRG1, NSUN4, NT5C2, NT5E, NTNG1, NUDT4, NUP153, NUP35, NUP50, NUPL1, NUSAP1, NUSAP1, ODF2, OS9, OSBPL6, OSMR, P4HA1, P4HA1, P4HB, PABPC1, PAK4, PAPD4, PAPD4, PAPD4, PCBP2, PARD3, PARN, PARP1, PARP14, PARP4, PARVB, PCBP2, PCBP4, PCBP4, PCDHGB3, PCGF3, PCGF3, PDLIM7, PCM1, PCMTD2, PCNXL2, PCSK9, PDE4A, PDE7A, PDXDC1, PEPD, PEX5, PFKP, PHF19, PHF8, PHRF1, PHRF1, PHTF2, PHTF2, PI4K2A, PIEZO1, PIGU, PIK3C2B, PITPNA, PITPNB, PITPNM1, PLAU, PLAU, PLEKHB2, PLEC, PMS1, PLSCR3, PLXNB2, PLXNC1, PMS1, POU2F1, POLE3, POLR3D, POSTN, POU2F1, PPAPDC1A, PPARA, PPARA, PPP6R1, PPHLN1, PPIP5K1, PPP1R12A, PPP6R2, PRKACB, PRKDC, PRMT1, PRNP, PRSS23, PSMA4, PTK2B, PSMC1, PSMD6, PTPN14, PTPN14, PUF60, PUS7, PVR, PXN, QKI, RAB23, RAB23, RAD23B, RAB2B, RAB34, RAD1, RAD23B, RALB, RAP1A, RAP1GDS1, RARG, RASSF8, RASSF8, RBCK1, RBCK1, RBFOX2, RBFOX2, RBM10, RCC1, RFTN1, RNF19A, RFWD2, RGS10, RGS3, RIF1, RNF14, RNF19A, RNF38, RNFT1, RPL10, RPS6KC1, RRBP1, RWDD4, RWDD4, SAR1A, SAMD9, SAMD9L, SART3, SCAF4, SCAF4, SCAF8, SCD, SCLT1, SCO1, SDCBP, SEC14L1, SEC22A, SEC24B, SEC61A1, SEPT9, SERPINE2, SF1, SF1, SH3RF1, SGOL2, SLC25A17, SKIL, SLC25A17, SLC39A3, SLC41A1, SLC4A4, SLC7A6, SLC7A8, SMARCA4, SMARCC2, SMC4, SMC6, SMCHD1, SMG1, SMYD3, SMPD4, SMYD3, SMYD5, SNAP23, SNHG16, SNX14, SOCS2, SON, SOS2, SPATA20, SPATS2, SPG20, SPRED2, STAU1, SQLE, SQRDL, SQSTM1, SRCAP, SREBF1, SREBF1, SREK1, SREBF1, STARD4, SRSF3, STAT1, STAT3, STAU1, STC2, STEAP2, STEAP2, STRIP1, STRN3, STX16, SUPT20H, SYNE1, SYNE2, SYNE2, SYT15, SYTL2, TACC1, TAF2, TANC2, TARBP1, TARBP1, TBC1D15, TARS, TBL2, TCF7L2, TENC1, TENM2, TEP1, TET3, TGFBR1, TFCP2, TGFBI, TGFBR1, TGFBRAP1, THADA, THAP4, THRB, TIMP2, TJP2, TLE3, TLK1, TMEM154, TMEM47, TMEM47, TNKS1BP1, TMEM63A, TNC, TNFAIP3, TNFRSF12A, TNS1, TNIP1, TNPO3, TNS1, TNS3, TOE1, TOMM40, TOMM5, TOMM5, TRAF3, TOPORS, TP53INP1, TRAF3, TRAK1, TRAPPC12, TRIB1, TRIM2, TRIM23, TRIM26, TRIM28, TRIM65, TRIM65, TRMT1L, TRIM65, TSC2, TRPS1, TSC2, TSHZ1, TSPAN2, TTC7A, TUBB2C, TUBB3, TXNL1, TXNRD1, TXNRD1, UBE2G2, U2SURP, UBAP2L, UBAP2L, UBE2V1, UBE2G2, UBE2V1, UBQLN4, UCHL5, UHMK1, UHRF1BP1L, UNC5B, USP19, USP7, VANGL1, VANGL1, VIPAS39, VARS2, VCL, VPS13A, VPS29, VWA8, VPS51, VWA8, WDR19, WDR37, WDR48, WIPF1, WIPF1, WWTR1, WNT5B, WSB1, WSB1, XIAP, WWTR1, XRN2, YAP1, YES1, YPEL5, YPEL5, YTHDF3, Z24749, ZAK, ZBTB10, ZBTB24, ZBTB7A, ZC3H12C, ZC3H14, ZC3H18, ZCCHC11, ZEB1, ZEB2, ZFAND1, ZFAND5, ZFAND5, ZMIZ1, ZHX3, ZMIZ1, ZMYM2, ZMYM2, ZNF219, ZNF12, ZNF148, ZNF219, ZNF227, ZNF24, ZNF268, ZNF28, ZNF281, ZNF335, ZNF37A, ZNF37BP, ZNF395, ZNF583, ZNF621, ZNF652, ZNF655, ZNF674, ZNF74, ZNF764, ZNF778, ZNF780A, ZNF827, ZNF839, or ZNF91. 
     
     
         35 . The method of  claim 34 , wherein the RNA sequence comprises exons, one or more introns, a 5′ splice site, a branch point, and a 3′ splice site; and wherein the 5′ splice site comprises the REMS and is upstream of the branch point and the 3′ splice site. 
     
     
         36 . The method of  claim 34 , wherein the REMS is endogenous. 
     
     
         37 . The method of  claim 34 , wherein the REMS is non-endogenous. 
     
     
         38 . The method of  claim 34 , wherein the cell is in a cell culture or cell lysate. 
     
     
         39 . The method of  claim 34 , wherein the REMS comprises the sequence ANGAguragu (SEQ ID NO: 4), wherein r is A or G and N is any nucleotide. 
     
     
         40 . The method of  claim 34 , wherein the precursor RNA results from aberrant expression of the gene. 
     
     
         41 . The method of  claim 40 , wherein aberrant expression is an abnormal down regulation of an RNA transcript in the cell relative to a corresponding healthy cell. 
     
     
         42 . The method of  claim 40 , wherein the cell is (a) from a cell line having an aberrant amount of an RNA transcript for the gene or; (b) from a subject with a disease involving an aberrant amount of an RNA transcript for the gene. 
     
     
         43 . The method of  claim 34 , wherein the gene is ABHD10, APLP2, ARMCX6, COL1A1, COL1A2, COL3A1, COL5A2, DIAPH3, ERGIC3, FADS2, FN1, FOXM1, GALC, GGCT, LAMA2, LARP7, MADD, PARP1, PRKDC, RCC1, STRN3, or VPS29.