Chapter 5 Confront our list of candidate to POSTAR database to identify potential regulator.

POSTAR is a database gathering multiple datasets on post-transcriptional gene regulation from experiments such as CLIP, PAR-CLIP, HITS-CLIP and AGO-CLIP, for various organisms, including Homo sapiens and Mus musculus.

In this report, we explore their database looking for RNA binding sites identified on our list of candidate post-transcriptionnaly regulated gene transcripts.

##Defining genes genomic ranges.

We use the package GenomicRanges to filter the POSTAR dataset with the genomic coordinates of our list of candidate genes.

5.1 Interactions with RNA binding proteins

We note that, with this approach, Celf1 is not found to be associated with eye’s abnormal development. (2018 paper, Siddam et al.), could we improve this approach using pubmed text mining?

Once we imported the dataset, we can check on the reported RBP for our list of genes:

Table 5.1: Table of known association of our candidate genes with RBP
RBP association
Apc Agtpbp1, Anapc1, Ankrd28, Anks1, Anp32a, Ap2a2, Appbp2, Atf7ip, AU040320, Bcas2, Bicd1, Camk2g, Ccnk, Ckap5, Clasp2, Clec16a, Cryzl1, Csnk1a1, Ctnnd2, Dennd1b, Dhx30, Dicer1, Dnmt3a, Eif4a2, Fads1, Foxk2, Golga1, Gpatch8, Grid1, H13, Hmg20a, Hnrnpc, Itfg1, Kif5c, Lims1, Lrrc58, Map2, Map4k4, Mark3, Mast2, Mcu, Mgrn1, Myo5a, Naa35, Ncoa2, Nectin1, Nhsl1, Nptn, Nsmce2, Pde10a, Pitpnc1, Pja2, Pkp4, Pten, Pum2, Rab28, Ranbp3, Rtn1, Slit3, Smg7, Son, Sorbs2, Sort1, Spast, Ss18, Stk38, Tbl1xr1, Tmcc1, Tmem30a, Tra2a, Trim2, Trim24, Ubn2, Ubr3, Uhrf2, Wac, Wdr7, Zc3h14, Zeb1, Zgpat, Zhx2, Zzef1
Celf2 Ascc2, Atf7ip, Atg10, Chka, Clasp2, Dnmt3a, Gpatch8, Gpr107, Hmg20a, Hnrnpc, Kif5c, Map4k4, Mark3, Ncoa2, Nptn, Nsmce2, Pde10a, Ppp1r13b, Pum2, Slit3, Tbl1xr1, Tmcc1, Ubn2, Usp36, Wac, Wnk1, Zeb1
Cirbp Ankrd28, Ckap5, Clasp2, Cnbp, Csnk1a1, Derl1, Eif4a2, Gpatch8, Gspt1, H1f0, Lrrc58, Map4k4, Mark3, Myo1e, Myo5a, Nid1, Nptn, Pten, Pum2, Purb, Rnf11, Scpep1, Sfr1, Son, Sparc, Tmem30a, Vmp1
Cpsf6 Eif4a2, Son, Sparc
Crebbp Eif4a2, Itm2b, Sparc
Elavl1 Purb
Ezh2 8030462N17Rik, Agtpbp1, Anapc1, Ankrd28, Anks1, Ap2a2, Appbp2, Ash2l, Atf7ip, Atg2b, Camk2g, Ccnk, Cdc123, Chka, Ckap5, Clasp2, Clec16a, Cpped1, Crybg3, Csnk1a1, Ctnnd2, Dennd1b, Dhx30, Dhx8, Edem3, Eif4a2, Eif4ebp1, Eif4enif1, Gnl3, Gpatch8, Gpr107, Gspt1, Hat1, Hnrnpc, Itgb5, Itsn2, Jmy, Klhl22, Lims1, Map4k4, Mark2, Mark3, Mast2, Mcu, Mnat1, Myo1e, Naa35, Ncoa2, Ndufaf2, Nectin1, Nfx1, Nhsl1, Nptn, Nsmce2, Pitpnc1, Pkp4, Polr2b, Ptdss2, Pten, Pum2, Ranbp3, Rpa1, Rprd2, Rps24, Sec62, Slc25a13, Slc7a1, Smg7, Son, Ss18, Stk38, Tbl1xr1, Tmcc1, Tra2a, Trim24, Ttc39b, U2af1, Ubn2, Ubr3, Uhrf2, Vmp1, Vps53, Wac, Wasf2, Wdr35, Wdr7, Wnk1, Xrcc4, Yy1, Zc3h14, Zeb1, Zfp91
Fus 8030462N17Rik, Aco2, Afg3l2, Agtpbp1, Amph, Anapc1, Ankrd28, Anks1, Anp32a, Ap2a2, Atf7ip, Atg2b, Atp5c1, Atp6v0a2, Bcas2, Bicd1, Birc2, Camk2g, Chka, Ckap5, Clasp2, Clec16a, Cltb, Cnbp, Commd3, Cryzl1, Csnk1a1, Ctnnd2, Dennd1b, Dhx30, Dicer1, Dmxl2, Dnmt3a, Edem3, Eif4a2, Eif4enif1, Exoc6, Fads1, Fhl1, Fkbp8, Foxk2, Glt8d1, Gnl3, Gpatch8, Gpr107, Grid1, Gspt1, H13, Hacd1, Hmg20a, Hnrnpc, Ift57, Itfg1, Itm2b, Itsn2, Jmy, Kif5c, Lims1, Lonp2, Lrrc58, Map2, Map4k4, Mark2, Mark3, Mast2, Mcu, Med14, Mgrn1, Myl6, Myo5a, Naa35, Napg, Ncoa2, Nfx1, Nhsl1, Nptn, Nsmce2, Pde10a, Pex13, Pigk, Pip5k1b, Pitpnc1, Pja2, Pkp4, Pld3, Pofut1, Ppp1r13b, Prkar1b, Pten, Pum2, Purb, Rab28, Rab3gap2, Rad54l2, Rmnd5a, Rnf11, Rnf14, Rprd2, Rtn1, Saraf, Sdha, Sec62, Selenot, Slit3, Smg7, Son, Sorbs2, Sort1, Sparc, Spast, Stk38, Tbl1xr1, Tmcc1, Tmem30a, Tra2a, Trim2, U2af1, Uba5, Ubn2, Ubr3, Uhrf2, Usp36, Vmp1, Wac, Wdr7, Wnk1, Yaf2, Yy1, Zc3h14, Zeb1, Zfyve1, Zgpat, Zzef1
Mbnl1 Fkbp1a, Itm2b, Lims1, Lrrc58, Nptn, Pja2, Sparc, Wasf2, Wnk1
Mbnl2 Nptn, Rtn1
Msi2 Acadl, Acox1, Arf6, Atp6v0a2, Csnk1a1, Edem3, Eif4a2, H1f0, Irf2bp2, Itm2b, Lrrc58, Mcu, Pcyt1a, Pten, Pum2, Purb, Rmnd5a, Saraf, Scpep1, Sdha, Selenot, Son, Tbl1xr1, Tmem30a, Vmp1, Wac, Wasf2, Zzef1
Nova1 Clasp2, Ctnnd2, Kif5c, Map2, Trim2
Nova2 Clasp2, Ctnnd2, Grid1, Kif5c, Map2, Map4k4, Nptn, Sorbs2, Trim2
Pabpc1 Afg3l2, Bcas2, Cnbp, Csnk1a1, Eif4ebp1, Fam32a, Fundc2, Glrx5, Gspt1, Gtf2h1, Hat1, Mrpl15, Mrps23, Npm3, Nubp2, Scpep1, Sdha, Sh3bgrl3, Slc7a1, Snrnp200, Ssr4, Tpi1, Vmp1, Wdr7
Ptbp2 Itfg1, Mast2, Nhsl1, Rab28, Rtn1, Tbl1xr1, Tmcc1, Trim24, Ubn2
Rbfox1 Ctnnd2, Gpatch8, Map2, Nptn, Pde10a, Pja2, Purb, Rnf11, Rtn1, Tmem30a, Zeb1
Rbfox2 8030462N17Rik, Agtpbp1, Ak4, Amph, Anapc1, Ankrd28, Anks1, Ap2a2, Appbp2, Arf6, Ash2l, Atf7ip, Atg10, Atp5c1, Axin1, Banf1, Camk2g, Cdc123, Chka, Churc1, Ckap5, Clasp2, Cnbp, Cpt1a, Cryz, Cryzl1, Csnk1a1, Dennd1b, Dicer1, Dmxl2, Eif4a2, Eif4ebp1, Eif4enif1, Fkbp1a, Foxk2, Gnl3, Gpatch8, Gpr107, Grid1, Gspt1, Gtf2a1, Gtpbp4, H13, Hat1, Hmg20a, Hnrnpc, Irf2bp2, Itfg1, Itsn2, Klhl22, Lims1, Llph, Lmf1, Lonp2, Lrrc1, Lrrc58, Map2, Map4k4, Map9, Mark2, Mark3, Mast2, Mcu, Med14, Mgrn1, Mlf2, Mnat1, Mphosph8, Mrpl15, Mrps18a, Mrps31, Myo1e, Myo5a, Nacc1, Ncoa2, Ndufaf2, Nfx1, Nptn, Nsmce2, Pak4, Pde10a, Pde6d, Pfdn2, Pitpnc1, Pja2, Pkp4, Plbd2, Pnkd, Pole4, Polr2b, Prmt7, Pten, Pum2, Purb, Rab3gap2, Rad54l2, Ranbp3, Rmnd5a, Rnf114, Rpa1, Rprd2, Rps24, Rsl1d1, Rtn1, Scpep1, Sdha, Sec62, Slc25a13, Slc7a1, Slit3, Smg7, Snrnp200, Snrpa, Snx8, Son, Sparc, Ss18, Stk38, Tbcel, Tbl1xr1, Tigar, Tmcc1, Tmem205, Tmem30a, Tomm20, Tra2a, Trim2, Trim24, Trit1, Tsr1, Ttc39b, Txnl4a, U2af1, Ube2z, Ubn2, Ubr3, Uhrf2, Usp36, Usp40, Utp4, Vmp1, Wac, Wasf2, Wdr35, Wdr4, Wdr7, Wnk1, Xrcc4, Yy1, Zc3h14, Zeb1, Zfp91, Zfyve1, Zzef1
Rbfox3 Camk2g, Ctnnd2, Gpatch8, Itm2b, Map2, Nptn, Pde10a, Pja2, Pld3, Purb, Rnf11, Rtn1, Tmem30a, Zeb1
Rbm10 6030458C11Rik, Aco2, Acox1, Anapc1, Anxa3, Ap2a2, Appbp2, Ascc2, Ash2l, Atf7ip, Atp6v0a2, Camk2g, Chka, Ckap5, Clasp2, Clcn7, Cnbp, Cryzl1, Csnk1a1, Dda1, Derl1, Dhx30, Dicer1, Dus2, Eif4a2, Eif4enif1, Fads1, Gga3, Gnl3, Golga1, Gpatch8, Gspt1, Hnrnpc, Ik, Ilk, Ipo13, Lims1, Lrrc58, Map4k4, Mark2, Mark3, Mast2, Med14, Mlf2, Mphosph8, Mrps18b, Myl6, Myo5a, Nelfe, Nfx1, Nptn, Pkp4, Pofut1, Polr3c, Ppp6r1, Prmt7, Pum2, Rab3gap2, Ranbp3, Rnps1, Rpa1, Rprd2, Rps10, Rps24, Rps6kb2, Rrp12, Rsl1d1, Scpep1, Sdha, Slc7a1, Smg7, Snrnp200, Snx17, Son, Sparc, Ssr4, Sympk, Timm50, Tomm20, Tra2a, Tsr1, Ttc39b, U2af1, Ube2z, Ubr3, Uhrf2, Usp36, Usp40, Utp4, Vmp1, Wdr74, Wnk1, Zfp143, Zzef1
Rbm3 Purb, Son
Srsf1 Anapc1, Ankrd28, Ckap5, Csnk1a1, Eif4a2, Map4k4, Pten, Pum2, Son, Sparc, Tra2a, Ubr3, Uhrf2, Vmp1, Wac, Wnk1
Srsf2 Anapc1, Ankrd28, Anxa3, Ap2a2, Atg2b, Chka, Ckap5, Clcn7, Cnbp, Csnk1a1, Eif4a2, Fads1, Gga3, Gnl3, Gpatch8, H1f0, Itm2b, Map4k4, Mark3, Mthfr, Myl6, Myo5a, Nfx1, Phf10, Pten, Pum2, Rab24, Ranbp3, Rpa1, Scpep1, Sdha, Sec62, Son, Sparc, Stk38, Tmem30a, Tra2a, Txnl4a, Ubr3, Uhrf2, Usp40, Vmp1, Wnk1, Zeb1, Zgpat
Srsf3 Abcg2, Csnk1a1, Eif4a2, Gpatch8, Med14, Pten, Smg7, Son, Wasf2, Wnk1
Srsf4 Eif4a2, Gnl3, Pten, Son
Taf15 Map2
Tardbp 8030462N17Rik, Agtpbp1, Amph, Anapc1, Ankrd28, Anks1, Anp32a, Ap2a2, Appbp2, Arhgap24, Atf7ip, Atg2b, Atp5c1, Atp6v0a2, AU040320, Axin1, Bcas2, Bicd1, Birc2, Camk2g, Chka, Ckap5, Clasp2, Clec16a, Cryzl1, Csnk1a1, Ctnnd2, Dennd1b, Dhx8, Dicer1, Dmxl2, Dnmt3a, Dus2, Edem3, Eif4a2, Exoc6, Fkbp8, Foxk2, Gan, Gmeb1, Golga1, Gpatch8, Grid1, Gtf2a1, Gtpbp4, Hacd1, Hmg20a, Hnrnpc, Ipo13, Irf2bp2, Itfg1, Jmy, Kif5c, Lims1, Map2, Map4k4, Mark2, Mark3, Mast2, Mcu, Mfn2, Mgrn1, Mnat1, Mydgf, Myo5a, Nacc1, Ncoa2, Nhsl1, Nptn, Nsmce2, Pde10a, Pigk, Pitpnc1, Pja2, Pkp4, Pnkd, Ppp1r13b, Prkar1b, Ptdss1, Pten, Pum2, Rab3gap2, Rad54l2, Rmnd5a, Rprd2, Rtn1, Sec62, Selenot, Slit3, Smg7, Son, Sorbs2, Sort1, Sparc, Spast, Ss18, Stk38, Sympk, Tbl1xr1, Tmcc1, Tmem30a, Tra2a, Trappc10, Trim2, Trim24, Ubn2, Ubr3, Uhrf2, Usp36, Usp40, Vps53, Wac, Wasf2, Wdr7, Wnk1, Yipf6, Yy1, Zc3h14, Zeb1, Zfyve1, Zzef1
U2af2 Agtpbp1, Anapc1, Ankrd28, Ap2a2, Appbp2, Ascc2, Ash2l, Atf7ip, Atg2b, Atp5c1, Bcap29, Bicd1, Camk2g, Cdc123, Cdk11b, Chka, Ckap5, Clasp2, Clec16a, Cnbp, Commd3, Cryzl1, Csnk1a1, Ctnnd2, Dhx30, Dicer1, Dmxl2, Dnmt3a, Edem3, Eif4a2, Eif4enif1, Fhl1, Foxk2, Gga3, Glt8d1, Gnl3, Golga1, Gpatch8, Grid1, Gspt1, Gtf2a1, Gtf2h1, Gtpbp4, H13, Hnrnpc, Ift172, Ik, Itfg1, Itsn2, Jmy, Kif5c, Lims1, Lrrc58, Map2, Map4k4, Mark2, Mark3, Mast2, Med14, Myo5a, Naa35, Ncoa2, Ncstn, Nfx1, Nptn, Pde10a, Pja2, Pkp4, Pten, Pum2, Rab3gap2, Rnf14, Rps24, Rrp12, Rsl1d1, Rtn1, Slit3, Smg7, Snrnp200, Son, Sorbs2, Sort1, Spast, Stk38, Sympk, Tbl1xr1, Tmcc1, Tmem30a, Tra2a, Trim2, Trim24, Tsr1, U2af1, Ubn2, Ubr3, Uhrf2, Usp36, Utp4, Vdac3, Vmp1, Wac, Wdr7, Wnk1, Yy1, Zc3h14, Zeb1, Zfp91, Zzef1
Ythdc2 8030462N17Rik, Adipor1, Agtpbp1, Anapc1, Ankrd28, Anks1, Ap2a2, Appbp2, Arf6, Ash2l, Asrgl1, Atf7ip, Atg2b, Atp6v0a2, AU040320, Axin1, Bcap29, Bcl7b, Birc2, Brap, Ccnk, Chka, Ckap5, Clasp2, Clec16a, Cnbp, Crat, Crybg3, Csnk1a1, Cstf1, Ddx20, Ddx25, Dennd1b, Derl1, Dhx30, Dhx8, Dmxl2, Edem3, Eif4a2, Faap100, Fbxw5, Fkbp1a, Fyco1, Gan, Gcc1, Gid4, Gle1, Glt8d1, Golga1, Gpatch8, Gpr107, Gtf2a1, Gtf2h1, H13, Hadha, Hnrnpc, Ift172, Ipo13, Itfg1, Itm2b, Jmy, Lmf1, Lrrc1, Lrrc58, Mark2, Mark3, Mast2, Mfn2, Mipep, Mnt, Mphosph8, Myo5a, Naa35, Ncoa2, Ncstn, Ndufaf3, Nek4, Nelfe, Nhsl1, Nol8, Nubp2, Oplah, Pcyt1a, Pde10a, Pgp, Pja2, Pkp4, Plbd2, Pnpla7, Ppp2cb, Ppp4c, Prmt7, Ptdss2, Pten, Pum2, Purb, Pwp1, Rab28, Rab3gap2, Rad54l2, Ranbp3, Rhbdd3, Rmnd5a, Rnf11, Rnf114, Rnf14, Rpa1, Rprd2, Rrp12, Rtn1, Rundc1, Saraf, Scpep1, Sdha, Selenot, Slc7a1, Smg7, Snrnp200, Son, Sort1, Sparc, Spast, Stk38, Sympk, Tbcel, Tbl1xr1, Tmcc1, Tmem30a, Tomm40, Tra2a, Trappc10, Trim24, Ttc12, Ttc39b, Tut1, Ube2j1, Ubn2, Ubr3, Wac, Wasf2, Wdr35, Wdr7, Wnk1, Yy1, Zc3h14, Zfp91, Zfyve1, Zzef1
Yy1 Eif4a2, Gpatch8, Mark2, Nectin1, Pitpnc1, Pkp4, Sparc, Wnk1, Yy1

###Experiments

We are continualy updating a list of our candidate ptx regulated genes or associated reported RNA binding protein known or not to be associated with eye’s related phenotype.

5.2 Interactions with micro-RNA

POSTAR database contain also AGO-CLIP which indicates binding sites of miRNA on transcripts:

MicroRNAs (miRNAs) play critical roles in the regulation of gene expression. However, since miRNA activity requires base pairing with only 6-8 nucleotides of mRNA, predicting target mRNAs is a major challenge. Recently, high-throughput sequencing of RNAs isolated by crosslinking immunoprecipitation (HITS-CLIP) has identified functional protein-RNA interaction sites. Here we use HITS-CLIP to covalently crosslink native Argonaute (Ago) protein-RNA complexes in mouse brain. This produced two simultaneous datasets—Ago-miRNA and Ago-mRNA binding sites—that were combined with bioinformatic analysis to identify miRNA-target mRNA interaction sites. Ago HITS-CLIP provides a general platform for exploring the specificity and range of miRNA action in vivo, and identifies precise sequences for targeting clinically relevant miRNA-mRNA interactions. Chi et al. (2009)

The datasets for AGO-CLIP in POSTAR are only targetting Ago2.

References

Chi, Sung Wook, Julie B. Zang, Aldo Mele, and Robert B. Darnell. 2009. “Argonaute HITS-CLIP decodes microRNA-mRNA interaction maps.” Nature 460 (7254). Nature Publishing Group: 479–86. https://doi.org/10.1038/nature08170.