Supplementary Figure S1 COX7RP mrna/gapdh COX activity (OD 45 nm/mg protein) Relative DNA amount COX7RP mrna/gapdh a c pcxn2-flag-cox7rp CAG Flag CMV enhancer Chiken b-actin promoter 1..8.6 COX7RP Muscle pa Rabbit b-globin polya signal d b kb 1.5 1.2.9.7.5.3 1..8.6 BAT.4.4 e.2 KO KO.7.6.5 f 3. 2.5 2..2 KO KO *.4.3.2.1 1.5 1..5 1 2 3 4 1 2 3 4 (Days) Supplementary Figure S1. Generation of COX7RP transgenic () mice. a, Schematic representation of the COX7RP transgene. b, Genotyping of COX7RP- mice. Representative litters containing COX7RP transgene were shown. Primers specific for the transgene were used to amplify the allele (6 bp). c and d, Overexpression of COX7RP in COX7RP- mice. mrnas of endogenous Cox7rp and introduced human COX7RP were quantified in quadriceps femoris muscles (c) and BAT (d) simultaneously by qpcr using common primers for mouse and human., P <.1; Dunnett s post hoc test. e, Increase in COX activity in COX7RP- MEFs. COX activity was assessed using MEFs from and COX7RP- mice. Data are presented as means ± s.d. (n = 3). *, P <.5 for versus COX7RP- ; Student s t-test. f, Upregulation of growth in COX7RP- MEFs. Data are presented as means ± s.d. (n = 3). *, P <.5,, P <.1for versus COX7RP- at each indicated time point; Student s t-test.
Supplementary Figure S2 Quadriceps femoris muscle /body weight Body weight (g) BAT/body weight a b 3 25 2 15 1 5.1 KO KO * c.8.6.4.2.1.8.6.4.2 KO KO * KO KO Supplementary Figure S2. Decreased skeletal muscle weight and increased BAT weight in Cox7rpKO mice. a, Body weight of 4-month-old mice (a) with genotypes, Cox7rpKO (KO, n = 9), COX7RP- (, n = 1), COX7RP-: Cox7rpKO (KO, n = 9), and (n = 7), were measured. b and c, Quadriceps femoris muscle (b) and BAT (c) was dissected and weight of these tissues were adjusted with corresponding body weight and data are presented as means ± s.d. *, P <.5,, P <.1; Dunnett s post hoc test.
Supplementary Figure S3 COX activity (O.D. 45 nm/mg protein) 3 2 * * 1 Cox7rp: Muscle: KO KO KO Supplementary Figure S3. Decreased COX activity in muscles of Cox7rpKO mice. The COX activity of quadriceps femoris, gastrocnemius and heart was measured from the tissue homogenates. Data are presented as means ± s.d. (n = 3). *, P <.5,, P <.1 for versus KO in each muscular tissue; Student s t-test.
Supplementary Figure S4 After 4 min KO After 7 min KO KO After 4 min KO After 7 min Supplementrary Figure S4. Compromised exercise performance in Cox7rpKO mice. Four-monthold Cox7rpKO (KO), COX7RP- (), COX7RP-:Cox7rpKO (KO) and mice were subjected to a forced treadmill exercise test. Movie captures at 4 and 7 min after the forced treadmill exercise test. Cox7rpKO mice showed exhaustion after 4 min.
Supplementary Figure S5 VO 2 (ml/min/g) VCO 2 (ml/min/g) RQ.1 *.8.8.6.8.6.4.4.6.4.2.2.2 Cox7rp: KO KO KO KO KO KO Supplementary Figure S5. Decrease in O 2 consumption rate in Cox7rpKO mice in the steady state. CO 2 production, O 2 consumption and respiratory quotient (RQ) were analyzed for 1 h. Data are presented as means ± s.d. (n = 7 or 8). *, P <.5,, P <.1; Dunnett s post hoc test.
Supplementary Figure S6 mrna/ GAPDH Pparα Pparγ Pparδ Pgc-1α Pcg-1β Errα Errβ Errγ Nrf1 Tfam.2.15 Cox7rpKO.1.5 Supplementary Figure S6. Downregulation of transcriptional regulatory factors associated with mitochondrial function in Cox7rpKO mice. qpcr analysis was performed using gene-specific primers with total RNAs prepared from BAT of and Cox7rpKO male mice. Data are presented as means ± s.d. (n = 3). *, P <.5,, P <.1; Student s t-test.
Supplementary Figure S7 SDS-PAGE SDS-PAGE SDS-PAGE SDS-PAGE a BN-PAGE b BN-PAGE I/III 2 /IV n III 2 /IV n IV 2 IV I/III 2 /IV n III 2 /IV n 2.8 79.2 (%) WB: 73. 27. (%) 46 UQCRC2 46 38 NDUFA9 38 IV 2 IV WB: UQCRC2 NDUFA9 26 19 (%) 3. 3. 6. 88. COX4 COX7RP 26 19 (%) 31.5 28.8 18.9 2.8 COX4 COX7RP c BN-PAGE 293T/vec d BN-PAGE 293T/COX7RP I/III 2 /IV n III 2 /IV n 22.5 77.5 46 38 26 24.9 75.1 (%) (%) WB: UQCRC2 NDUFA9 RISP 46 38 26 I/III 2 /IV n III 2 /IV n 66.7 33.3 72.4 27.6 (%) (%) WB: UQCRC2 NDUFA9 RISP 19 19 293T/vec 293T/COX7RP Supplementary Figure S7. COX7RP stimulates the assembly of mitochondrial respiratory chain supercomplexes. Mitochondrial proteins of 293T cells transfected with empty vector (a and c) and COX7RP (b and d) were solubilized with digitonin in the concentration of 2 g/g protein (a and b) or.5 g/g protein (c and d), and subjected to BN-PAGE followed by second-dimensional SDS- PAGE. Western blot analysis was performed with antibodies for NDUFA9 of complex I, UQCRC2 of complex III, RISP of complex III, COX4 of complex IV, and COX7RP. Positions corresponding to mitochondrial supercomplex species I/III 2 /IV n, I/III 2, and III 2 /IV n, as well as dimerized complex IV (IV 2 ) and monomerized complex IV (IV) are indicated. Percentages of UQCRC2, RISP or COX4 signal intensities in each whole amount are indicated in the images.
Supplementary Figure S8 Fig. 1c 118 82 4 31 118 82 4 31 17 7 17 7 Fig. 4a 75 5 37 25 2 15 1 Fig. 4b 75 5 37 25 2 15 1 Fig. 4c 62 46 38 26 19 9 Fig. 4d 62 46 38 26 19 9 Supplementary Figure S8. Full length images of immunoblots.
Supplemantary Table S1. Downregulated pathway genes in the muscle of Cox7rpKO mice Term Count P value Genes Muscle protein 1 6.9E-13 Tnnt2, Myl7, Myl2, Tnnc1, Myl3, Myh7, Myh6, Tnni3, Tnni1, Tpm3 Cardiac muscle contraction Dilated cardiomyopathy 11 9.5E-11 Tnnt2, Myl2, Atp2A2, Tnnc1, Myl3, Ryr2, Myh7, Myh6, Cox7A2L, Tnni3, Tpm3 11 5.E-1 Tnnt2, Myl2, Atp2A2, Tnnc1, Myl3, Pln, Ryr2, Myh7, Myh6, Tnni3, Tpm3 Vmn2R43, Vmn1R125, Olfr76, Vmn2R42, Vmn1R148, Olfr331, Vmn1R121, Vmn2R26, Vmn2R-Ps6, Gm769, Olfr728, Vmn1R168, Acvr1C, Adrb3, Olfr36, Receptor 33 2.E-9 Olfr1333, Vmn1R93, Olfr26, Olfr1134, Olfr247, Vmn1R132, Olfr145, Vmn2R51, Vmn2R34, Olfr124, Vmn1R179, Olfr137, Olfr715, Vmn2R37, Olfr1287, Csprs, Vmn2R122, Vmn1R-Ps4, Chrm2, Vmn1R223, Olfr8, V1Rg1, Ryr2, Olfr329, Vmn1R191, Tshr, Olfr121, Vmn1R1 Hypertrophic cardiomyopathy 1 4.7E-9 Tnnt2, Myl2, Atp2A2, Tnnc1, Myl3, Ryr2, Myh7, Myh6, Tnni3, Tpm3 G-protein coupled receptor protein signaling pathway 3 1.7E-8 Vmn2R43, Vmn1R125, Olfr76, Vmn2R42, Olfr331, Vmn1R148, Vmn1R121, Vmn2R26, Vmn2R-Ps6, Olfr728, Vmn1R168, Adrb3, Olfr36, Olfr1333, Vmn1R93, Olfr26, Olfr1134, Olfr247, Vmn1R132, Olfr145, Vmn2R51, Vmn2R34, Olfr124, Vmn1R179, Olfr715, Olfr137, Vmn2R37, Olfr1287, Vmn2R122, Vmn1R-Ps4, Chrm2, Vmn1R223, Olfr8, V1Rg1, Olfr329, Vmn1R191, Tshr, Olfr121, Vmn1R1 G-protein coupled receptor 21 1.4E-6 Tnnt2, Myl7, Myl2, Tnnc1, Myl3, Myh7, Myh6, Tnni3, Tnni1, Tpm3 Cell surface receptor linked signal transduction 31 2.5E-6 Tnnt2, Myl7, Myl2, Tnnc1, Myl3, Myh7, Myh6, Tnni3, Tnni1, Tpm3 Transducer 21 2.6E-6 Tnnt2, Myl7, Myl2, Tnnc1, Myl3, Myh7, Myh6, Tnni3, Tnni1, Tpm3 Heart 4 6.3E-6 Tnnt2, Myl2, Atp2A2, Tnnc1, Myl3, Ryr2, Myh7, Myh6, Cox7A2L, Tnni3, Tpm3
Supplementary Table S2. Upregulated pathway genes in the muscle of Cox7rpKO mice Term Count P value Genes Amino-acid biosynthesis 4 1.3E-5 Pycr1, Aldh18A1, Asns, Psat1 Cellular amino acid biosynthetic process Amine biosynthetic process 4 2.2E-4 Pycr1, Aldh18A1, Asns, Psat1 4 1.E-3 Pycr1, Aldh18A1, Asns, Psat1 Oxidoreductase 7 1.6E-3 Mthfd2, Pycr1, Cyb5R1, Aldh18A1, Egln3, Impdh2, Srxn1 Glutamine family amino acid metabolic process Microtubule-associated protein MAP1B Organic acid biosynthetic process Carboxylic acid biosynthetic process L-type amino acid transporter Nitrogen compound biosynthetic process 3 6.1E-3 Pycr1, Aldh18A1, Asns 2 6.4E-3 Mtap1A, Mtap1B 4 6.6E-3 Pycr1 4 6.6E-3 Pycr1, Aldh18A1, Asns, Psat1 2 6.6E-3 Slc7A5, Slc7A11 5 8.9E-3 Pycr1, Aldh18A1, Asns, Psat1, Impdh2
Supplementary Table S3. Downregulated pathway genes in the BAT of Cox7rpKO mice Term Count P value Genes Mitochondrion 96 5.5E-17 Ldha, Pdp2, Aldh1L1, Nit2, Ehhadh, Ldhd, Bnip3, Echdc2, Echdc3, Car5B, Acss3, Mccc2, Pecr, Gpx1, Acss1, 933129D5Rik, Slc22A4, Gstz1,Tfb2M, Pxmp2, Prkaca, Slc25A1, Elovl6, Hmgcl, Rtn4Ip1, Hemk1, Brp44, Suox, Aldh6A1, Aco1, Aldh5A1, Lgals12, C3318D2Rik, Immp1L, Hagh, Sccpdh, Glul, Nme3, Ppm1K, Slc25A35, 533411D12Rik, Gm9568, Gpam, Slc27A2, Pcca, Mpst, Mavs, Me1, Ndufb3, Hsd17B1, Apool, Acadsb, Bcat2, Adhfe1, Abcd1, Hk2, Echs1, Cox7A2L, Acat2, Ccbl2, Acat1, Sfxn5, Acat3, Ivd, Fasn, Abcd2, Idh1, Aldh4A1, Mrpl18, Slc25A44, Cabc1, Slc25A42, Acsl5, Pdk1, Gpd2, Gpd1, Gcdh, Maob, Acaca, Acly, Acacb, Ucp1, Ndufa1, Tst, Acsm3, Pcx, Hmgcs2, Slc25A1, Hdhd3, Brp44L, Slc25A19, Acad11, Scp2, Mgst1, Acsm5, D1Jhu81E Oxidation reduction 59 3.9E-14 Sepx1, Steap4, Cyp2D1, Ldha, Aldh1L1, Ltbp2, Ehhadh, Ldhd, Fdft1, Gpx1, Pecr, P4Ha1, Gpx8, Rtn4Ip1, Aldh6A1, Suox, Cyp1A1, Aldh5A1, Aldh3B2, Cyp2E1, Cyp2B1, Cdo1, Dhdh, Dhrs7, C3318D2Rik, Sccpdh, H6Pd, Hsd11B1, Gm9568, Ndufb3, Me1, Hsd17B1, Acadsb, Adhfe1, Cyp2F2, Hsd3B7, Hsd17B12, Egln3, Egln1, Fmo5, Ivd, Fmo1, Fasn, Aldh4A1, Idh1, Aldh1A7, Adh6B, Gpd2, Gcdh, Gpd1, Maob, 4933437F5Rik, Cyp4V3, Ndufa1, Vat1L, Dio2, Dpyd, Acad11, Retsat Oxidoreductase 52 6.2E-13 Sepx1, Steap4, Cyp2D1, Ldha, Aldh1L1,Ehhadh, Ldhd, Fdft1, Gpx1, Pecr, P4Ha1, Gpx8, Aldh6A1, Suox, Cyp1A1, Aldh5A1, Cyp2E1, Cyp2B1, Cdo1, Dhdh, Dhrs7, Sccpdh, H6Pd, Hsd11B1, Gm9568, Me1, Hsd17B1, Acadsb, Adhfe1, Cyp2F2, Hsd3B7, Hsd17B12, Egln3, Egln1, Fmo5, Fmo1, Ivd, Fasn, Aldh4A1, Idh1, Aldh1A7, Gpd2, Gcdh, Gpd1, 4933437F5Rik, Maob, Cyp4V3, Vat1L, Dio2, Dpyd, Acad11, Retsat Fatty acid metabolic process Lipid metabolism 27 1.7E-11 18 1.E-1 Slc27A1, Acadsb, Ehhadh, Abhd5, Prkag2, Echs1, Echdc2, Pecr, Agpat6, Ptges, Elovl3, Acot11, Fasn, Elovl6, Ghr, Acsl5, Aldh5A1, Acaca, Adipor2, Acacb, Adipoq, Acsm3, Aacs, Slc27A2, Gpam, Acsm5, Mgst2 Gcdh, Ces3, Acadsb, Acaca, Echdc1, Echs1, Echdc2, Acacb, Acsm3, Mccc2, Ivd, Bche, 933129D5Rik, Acad11, Acsm5, Pcca, Au18778, Acsl5 Brown fat cell differentiation 12 2.1E-1 Cebpa, Adrb3, Aldh6A1, Rgs2, Slc2A4, Mrap, Lrg1, Nudt7, Bnip3, Ucp1, Adipoq, Arl4A Mitochondrion 56 1.E-9 Fat cell differentiation 15 1.3E-9 Transferase 79 5.8E-9 Mitochondrial part 42 1.3E-8 Ldhd, Echdc2, Bnip3, Echdc3, Car5B, Acss3, Mccc2, Acss1, Tfb2M, Elovl6, Rtn4Ip1, Hmgcl, Aldh6A1, Suox, Aldh5A1, Hagh, Immp1L, Ppm1K, Slc25A35, Gpam, Pcca, Mpst, Ndufb3, Mavs, Hsd17B1, Acadsb, Bcat2, Adhfe1, Echs1, Cox7A2L, Acat1, Sfxn5, Ivd, Mrpl18, Aldh4A1, Slc25A44, Cabc1, Slc25A42, Acsl5, Gpd2, Pdk1, Gcdh, Maob, Ucp1, Ndufa1, Acsm3, Tst, Pcx, Hmgcs2, Slc25A1, Slc25A19, Brp44L, Scp2, Acsm5, Mgst1, D1Jhu81E Cebpa, Aldh6A1, Steap4, Mrap, Bnip3, Ucp1, Adipoq, Gpx1, Retn, Adrb3, Slc2A4, Rgs2, Lrg1, Nudt7, Arl4A Nampt, Sephs2, Gstm6, Pmvk, Itpka, Pnp, Fdft1, Gstm7, Acvr1C, St3Gal1, St6Galnac6, Agpat6, St3Gal5, St3Gal4, Gstz1, Tfb2M, Prkaca, Agphd1, Pcyt2, Hemk1, Sgk2, Pfkl, Chpt1, Pnpla3, Cdkl5, Chst1, Prkd1, Pank3, Nme3, Dgat2, Pank1, Adk, 533411D12Rik, Gpam, Hs3St3B1, Mpst, Bcat2, Taldo1, Fut7, Pfkfb3, Pfkfb1, Abhd5, Mknk2, Mapkapk3, Hk2, Adrbk2, Acat2, Ccbl2, Acat1, Acat3, Gm135, Sbk1, Hnmt, Ptk2B, Fasn, Gys2, Uck1, Gsto2, Cabc1, Mettl7A1, Pdk1, Gsta3, Mogat1, B3Galt2, Acly, Tkt, Inmt, Dolk, Tst, Ntrk3, Hmgcs2, Pygl, Ntrk2, Gpt, Scp2, Mgst1, Nat8L, Mgst2, Nnmt Mavs, Ndufb3, Hsd17B1, Apool, Acadsb, Echs1, Bnip3, Cox7A2L, Acat1, Sfxn5, Mccc2, Acss1, Ivd, Aldh4A1, Slc25A1, Slc25A44, Slc25A42, Hmgcl, Acsl5, Gpd2, Pdk1, Gcdh, Suox, Maob, Ucp1, Ndufa1, Tst, Hagh, Acsm3, Immp1L, Pcx, Hmgcs2, Ppm1K, Slc25A1, Slc25A35, Slc25A19, Brp44L, Gpam, Pcca, Mgst1, Acsm5, Mpst
Supplementary Table S4. Upregulated pathway genes in the BAT of Cox7rpKO mice Term Count P value Genes Phosphoprotein 414 1.2E-2 Xrcc5, Naf1, Jub, Tubb2B, Plekhm2, Surf6, Tubb2A, Rusc2, L1Cam, Rpl22L1, Snora65, Kifc3, Lphn2, Actg1, App, Mak16, Rpl12, Ptprj, R3Hcc1, Ctnna1, Myh9, Sirpa, Jup, Ifi22B, Grb1, Pitpnm3, Aaas, Rcc2, Spag5, Jun, Eif2S2, Mybbp1A, Dcbld2, Pltp, Spp1, Pppde2, Rps24, Odc1, Kif3A, Ppfibp1, Gars, Atr, Rps8, Fnip2, Gcfc1, Rgs1, Parp9, Lasp1, Gas2L3, Slc2A1, Trpv2, Nap1L1, Atp1D, Gm8292, Hsf2, Spg2, Synj2, Myc, Arhgef2, Gm5643, Rap2C, Anp32B, Acta2, Arhgef6, Gmeb1, Slc3A2, Hn1, Clic1, Exosc1, Arhgef12, Flnb, Trmt61A, Flna, Arhgef1, Elmo1, Ccnd1, Tmsb4X, Stbd1, Them4, Wdr43, Srgap1, Aw1462, Reps1, Tbc1D9, Gpr65, Eri1, Nufip1, Abi2, Hk1, Rtkn, 9432K1Rik, Il7R, Igsf1, Sorbs3, Kirrel, Anks6, Armcx3, Tcea1, Exoc1, Mid1, Cpt1A, Gla, Plscr2, Phf16, Phldb2, Akna, Ctnnal1, Rbm3, Eif5, Slc7A5, Fntb, Nrcam, Unc5B, Ank2, Mdfic, Snd1, Slc2A1, Ddx21, Sptlc2, Stap1, Stk24, Baiap2, Actn1, Tmsb1, Tmem29, Mrto4, Hspb6, Mtap1A, Hspb8, Mtap1B, Bmp2K, Stmn1, Pam, Nr2C1, Dock2, Smarcb1, Gp49A, Mettl1, Jund, Sh3Tc2, Mrc1, Trp53, Hcn2, Nin, Myo1D, Golim4, Myo1F, Pold3, Plk4, Atf4, Ddx56, Slc7A2, Fabp3, Acox2, Cyb5R2, Fosl2, Atl1, Cldn5, Wwc1, Gabbr2, Acot6, Ptma, Sdc3, Slc1A4, Prmt3, Spry2, Wars, Prmt1, Grwd1, Hmox1, Sntb2, Loxl4, Gm5841, Cdk5Rap2, Lrrfip1, Nfil3, Dlg2, Sgk1, Sars, Stxbp1, Stxbp4, Hltf, Ncl, Slc7A11, Ipo4, Frmd4A, Ipo5, Ern1, Mapre2, Lcp1, Lcp2, Ablim2, Vars, Esyt2, Chd7, Atic, Inpp5J, Naip5, Gpnmb, Ehd4, 531439G7Rik, Slc12A4, Anxa1, Creb5, C3327C9Rik, Anxa4, Tab2, Pwp2, Pwp1, Cyba, Jak1, Rpp38, Dync1Li1, Sncg, 493422G4Rik, Stard3Nl, Ptpn23, Ptpn21, Pdlim1, Got2, Got1, Gab2, Cd44, 843419L9Rik, Stam, Zfp33, Ddx1, Matn2, C5Ar1, Stc2, Aars, Glce, Sfrs3, Baz1A, Pgm1, Lilrb4, Cdca7L, Nup43, Nek6, 543435G22Rik, Aldoc, Akap12, Sfpi1, Igf2Bp2, Chek2, Myo9A, Plaa, Fam65B, Sema5A, Slc11A1, Fam12A, Vrk1, Vrk2, Fcer1G, Emd, Tyrobp, Sash1, Lgals3, Crip2, Osbpl6, Eprs, Ptpn12, Hn1L, Pla2G4A, Atp2A3, Clec7A, Utp14A, Utp2, Chaf1B, Klf4, Nars, Anpep, Cpeb1, 1627N9Rik, Ckb, Blzf1, Rrp1B, Mtbp, Tubb5, Zfp238, Tubb6, Fam129B, Dock1, Fam129A, Agap1, Rbbp5, Zcchc11, Mbd2, Rad5, Rab11Fip5, Nol1, Farsb, Ltv1, Bid, Lims2, Slc39A1, Mif, Plcl2, Sqstm1, Bcl2, Aatf, Kif21B, Tes, Fyb, Plek, Aff3, Ilf3, Atp1A1, Npr3, Samd4, Iws1, Svil, Capg, Phgdh, Nop58, Nop56, Zc3Hav1, Wfs1, Ctps, Gabrb1, Mbip, Tlr7, Pus7L, Dysf, Tiam1, Gnl2, Odz2, Gnl3, Cars, Dars, Rrp9, Arntl, Tns3, 49356M7Rik, Lat2, Trim33, Fnbp1L, 4116, Mvp, Plxnc1, Blm, Agfg1, Ssh2, Itgb2, Fxyd5, Srf, Eif3C, Eif3A, Laptm5, Npm1, Stambpl1, Rnf11, Strbp, Entpd1, Tsr1, Brca2, Mafk, Coro1C, Epb4.1L4A, Wdr1, St5, Plekha1, Fam175A, Ppip5K2, Prrx1, Mtss1L, Ddr2, Bzw2, Ccdc41, Evi2A, Pcgf6, Zyx, Msn, Tuba1A, Tuba1B, Ttc39B, Atp8B4, Pilra, Lair1, G3Bp1, Mtap4, Mpp6, Foxj3, Palld, Krtcap2, Arhgap25, Dapk1, Cd84, Prkd2, Ddr1, Tars, Umps, Eya2, Prnp, Ppp1R15A, Cnn3, Tnc, Cyth4, Hat1, Tpm4, Rgs1, Cep57, m2, Lars, Thyn1, Camk2B, Cnn2, Il2Rg, Myof, Dctd, Ptprc, Ampd3, Fam6A, Sh3Bp4, Slc6A8, Sh3Bp2, Nfib Nucleolus 44 1.8E-11 Rpp38, Taf1A, Surf6, Utp15, Eri1, Nufip1, Snora65, Dimt1, G2E3, Mak16, Rrp1B, Mdfic, Grwd1, Hmox1, Npm1, D19Bwg1357E, Aatf, Zfp33, Ddx21, Rpl12, Gnl2, Gnl3, Trp53, Exosc8, Tsr1, Ilf3, Rrp9, Exosc1, Mbd2, Ncl, Pwp2, Mrto4, Dis3, Plk4, Ddx56, Eya2, Rcc2, Nol1, Nol11, Nop58, Nop56, Utp14A, Utp2, Mybbp1A, Wdr43 ncrna metabolic process Intracellular nonmembranebounded organelle Nonmembranebounded organelle AminoacyltRNA synthetase Ribosome biogenesis trna metabolic process Ribonucleoprotein complex biogenesis 35 3.3E-11 143 6.4E-11 143 6.4E-11 Rpp38, Naf1, Nars, Utp15, Eri1, Qtrt1, Vars, Pus7L, Iars, Dimt1, Wars, Wdr36, Rrp1B, Trdmt1, Mettl1, Lars, Cars, Yars, Exosc8, Zcchc11, Dars, Sars, Aars, Gars, Eprs, Exosc1, Rrp9, Trmt61A, Dis3, Tars, Ddx56, Pop1, Farsb, Utp14A, Dus4L Ctnnal1, Rpp38, Xrcc5, Dync1Li1, Sncg, Jub, Tubb2B, Surf6, Tubb2A, Pdlim1, Ptpn21, Rpl22L1, Snora65, Kifc3, Actg1, Actg2, App, G2E3, Mak16, Ank2, Mdfic, D19Bwg1357E, Ddx21, Zfp33, Rpl12, Gnl2, Gnl3, Kif5A, Actn1, Tmsb1, Rrp9, Ctnna1, Myh9, Mrto4, Jup, Baz1A, Rcc2, Fnbp1L, Spag5, Mtap1A, Mtap1B, Rps12, Stmn1, Mybbp1A, Nup43, 4116, Blm, Ssh2, Akap12, Myo9A, Itgam, Dock2, Eif3A, Trim66, Smarcb1, Npm1, Strbp, Emd, Rps24, Trp53, Kif3A, Nin, Tsr1, Myo1E, Myo1D, Myo1F, Syce2, Atr, 41163, Rps8, Coro1C, Plk4, Ddx56, Lasp1, Pcna, Epb4.1L4A, Wdr1, Utp14A, Utp2, Taf1A, Utp15, Pot1A, Cpeb1, Prmt3, Slc1A4, Spry2, Des, Gm8292, Rrp1B, Grwd1, Hmox1, Tubb5, Tubb6, Sntb2, Cdk5Rap2, Zyx, Msn, Tuba1A, Myc, Tuba1B, Dlg2, Arhgef2, Exosc8, Acta2, Mtap4, Exosc1, Mbd2, Palld, Ncl, Flnb, Rad5, Flna, Elmo1, Eya2, Sgcg, Frmd4A, Dnahc7B, Nol1, Nol11, Tmsb4X, Mapre2, Wdr43, Lcp1, Ablim2, Eri1, Nufip1, Abi2, Tpm4, Dimt1, Sorbs3, Chd7, Cep57, Aatf, Kif21B, Cep192, Ilf3, Mid1, Smc2, Lrrc49, Pwp2, Dis3, Svil, Nop58, Jak1, Nop56 Ctnnal1, Rpp38, Xrcc5, Dync1Li1, Sncg, Jub, Tubb2B, Surf6, Tubb2A, Pdlim1, Ptpn21, Rpl22L1, Snora65, Kifc3, Actg1, Actg2, App, G2E3, Mak16, Ank2, Mdfic, D19Bwg1357E, Ddx21, Zfp33, Rpl12, Gnl2, Gnl3, Kif5A, Actn1, Tmsb1, Rrp9, Ctnna1, Myh9, Mrto4, Jup, Baz1A, Rcc2, Fnbp1L, Spag5, Mtap1A, Mtap1B, Rps12, Stmn1, Mybbp1A, Nup43, 4116, Blm, Ssh2, Akap12, Myo9A, Itgam, Dock2, Eif3A, Trim66, Smarcb1, Npm1, Strbp, Emd, Rps24, Trp53, Kif3A, Nin, Tsr1, Myo1E, Myo1D, Myo1F, Syce2, Atr, 41163, Rps8, Coro1C, Plk4, Ddx56, Lasp1, Pcna, Epb4.1L4A, Wdr1, Utp14A, Utp2, Taf1A, Utp15, Pot1A, Cpeb1, Prmt3, Slc1A4, Spry2, Des, Gm8292, Rrp1B, Grwd1, Hmox1, Tubb5, Tubb6, Sntb2, Cdk5Rap2, Zyx, Msn, Tuba1A, Myc, Tuba1B, Dlg2, Arhgef2, Exosc8, Acta2, Mtap4, Exosc1, Mbd2, Palld, Ncl, Flnb, Rad5, Flna, Elmo1, Eya2, Sgcg, Frmd4A, Dnahc7B, Nol1, Nol11, Tmsb4X, Mapre2, Wdr43, Lcp1, Ablim2, Eri1, Nufip1, Abi2, Tpm4, Dimt1, Sorbs3, Chd7, Cep57, Aatf, Kif21B, Cep192, Ilf3, Mid1, Smc2, Lrrc49, Pwp2, Dis3, Svil, Nop58, Jak1, Nop56 14 9.E-9 Yars, Cars, Dars, Nars, Sars, Aars, Gars, Eprs, Vars, Iars, Wars, Tars, Lars, Farsb 22 2.8E-8 22 3.3E-8 24 5.5E-8 Naf1, Exosc8, Tsr1, Surf6, Utp15, Eri1, Rrp9, Exosc1, Mrto4, Dimt1, Dis3, Ddx56, Wdr36, Rrp1B, Ipo4, Npm1, Nop58, Aatf, Nop56, Gnl2, Utp14A, Znhit6 Rpp38, Yars, Cars, Nars, Dars, Sars, Aars, Gars, Eprs, Qtrt1, Vars, Trmt61A, Iars, Pus7L, Wars, Tars, Trdmt1, Mettl1, Farsb, Lars, Pop1, Dus4L Naf1, Exosc8, Tsr1, Surf6, Utp15, Eri1, Exosc1, Rrp9, Mrto4, Dimt1, Dis3, Ddx56, Eif3A, Wdr36, Prmt7, Rrp1B, Ipo4, Npm1, Nop58, Aatf, Nop56, Gnl2, Utp14A, Znhit6