Kudzora Kuratidzwa Kwemajini Muzvinhu Zvipenyu
Kudzora matauriro emajini inzira yekudzora kuti jini rinovhurwa riini, kupi, uye kuti jini rinovharwa riini mukati mesero. Kunyangwe masero ese ari muchipenyu chine masero akawanda aine DNA imwe chete, rudzi rwesero rega rega runogona kuita mabasa akasiyana - semuenzaniso, masero etsinga, masero emhasuru, uye masero echiropa. Misiyano iyi inoitika nekuda kwesarudzo yemajini: mamwe majini chete ndiwo anoshanda panguva dzakatarwa uye pasi pemamwe mamiriro. Kudzora matauriro emajini ndiyo hwaro hwakakosha hwekukura kwemwana ari mudumbu, kusiyana kwemasero, mhinduro dzezvakatipoteredza, uye kuchengetedza hutano hwemuviri (homeostasis). Kukanganiswa kwemutemo uyu kunogona kukonzera zvirwere zvakasiyana-siyana, kusanganisira kenza, matambudziko emetabolism, uye kusarongeka kwekukura.
Pfungwa huru: kubva kumajini kusvika kumapuroteni
Kutaurwa kwemajini kunowanzo reva kuyerera kwemashoko ehupenyu kubva kuDNA kuenda kuRNA uyezve kuenda kuprotein (pfungwa huru yebiology yemamorekuru). Zvisinei, kutaura kwemajini hakungogumiri pakugadzirwa kwemapuroteni chete: mamwe majini anogadzira maRNA anoshanda (semuenzaniso, rRNA, tRNA, kana microRNA) anoshanda zvakananga pasina kushandurwa kuita protein. Nekuti chigadzirwa chejini—protein kana RNA—chinosarudza chimiro nebasa resero, zvipenyu zvinoda sisitimu chaiyo yekutonga kuti majini ashande zvakanaka, akanangwa, uye akakodzera.
Kazhinji, kudzora kwekutaura kwemajini kunogona kuitika pamatanho akati wandei: (1) kutonga kwe epigenetic uye chimiro chechromatin, (2) kutonga kwetranscriptional, (3) kugadzirisa RNA mushure mekunyora, (4) kugadzikana kweRNA uye kutakurwa kwayo, (5) kutonga kwekushandura, uye (6) kugadziriswa kweprotein uye kuora kwayo. Danho rega rega rinopa "nzvimbo dzekudzora" dzinogona kushandiswa nesero kudzora kubuda kwekupedzisira.
Mutemo weEpigenetic: kudzora mukana wekuwana DNA
Chikamu chekutanga chekutonga iepigenetics, inova shanduko dzinokanganisa mashandiro emajini pasina kushandura kurongeka kweDNA base. Maitiro makuru e epigenetic anosanganisira DNA methylation, kugadziriswa kwehistone, uye kudzora chimiro chechromatin.
DNA methylation inowanzo itika pa cytosines munzvimbo dzeCpG uye inowanzo batanidzwa nekudziviswa kwekutaura kwemajini. Kana chinhu chinokurudzira chikasanganiswa ne methylation, zvinhu zvinonyorwa zvinova zvakaoma kusunga, zvichikonzera kudzikira kwekunyora. Kusiyana neizvi, demethylation inogona kuvhura mukana wekushanda kwemajini. Kugadziriswa kweHistone—senge acetylation uye methylation yemitsetse yehistone—kunochinja huwandu hwechromatin. Histone acetylation inowanzo "sunungura" chromatin (euchromatin), zvichiita kuti kunyorwa kwemajini kuve nyore, nepo mamwe marudzi ehistone methylation achigona kumanikidza chromatin (heterochromatin) uye kudzvinyirira kutaura.
Kudzora magenetikisi emasero kwakakosha pakusiyana kwemasero. Semuenzaniso, panguva yekukura kwemwana ari mudumbu, pakutanga masero akafanana "anovhara" maitiro chaiwo ekutaura kwemajini kuburikidza nezviratidzo zve epigenetic, nokudaro achichengetedza kuzivikanwa kwemasero sezvo masero achipatsanuka. Zvinhu zvakatipoteredza zvakaita sekudya kunovaka muviri, kushushikana, uye kusangana nemakemikari zvinogonawo kukanganisa epigenome, zvichitsanangura kuti nei zvinhu zvekunze zvichigona kuchinja kuratidzwa kwemajini kwenguva refu.
Mutemo wekunyora: basa revanokurudzira, vanosimudzira, uye zvinhu zvinonyora
Danho guru rekutonga nderekudzora manyorerwo eDNA, iro riri kutonga maitiro ekuumbwa kweRNA kubva kuDNA neRNA polymerase. MuEukaryotes, kunyorwa kwemanyorerwo kunowanzo tangira papromoter, DNA sequence apo transcription complex inoumbwa. Pamusoro pepromoter, kune zvinosimudzira uye zvinonyaradza—zvinhu zvinodzora zvinogona kuwedzera kana kuderedza mwero wekunyora, kunyangwe zviri kure nejini rinodzorwa. DNA inogona kupetwa kuita zvishwe, zvichibvumira zvinosimudzira kuti zvibatane nepromoter kuburikidza nemaprotein e linker.
Zvinhu zvinonyora mapuroteni zvinobatana kune mamwe maDNA sequences uye zvinodzora RNA polymerase activity. Kune zvinhu zvinonyora mapuroteni zvinodiwa kuti pave nekunyorwa kwemajini akawanda, uye zvinhu zvinonyora mapuroteni zvinongoshanda mumajini kana mumatishu chaiwo. Zvinhu zvakawanda zvinonyora mapuroteni zvinokanganiswa nemasaini emasero, akadai semahormone, zvinhu zvinokura, kana mamiriro ekushushikana. Kana chiratidzo chasvika, chinhu chinonyora mapuroteni chinogona kuvhurwa kuburikidza nephosphorylation, shanduko munzvimbo (semuenzaniso, kupinda munucleus), kana kusangana nevanoita kuti mapuroteni ashande pamwe nevanoita kuti mapuroteni ashande pamwe chete.
Mumabhakitiriya, kudzorwa kwetranscriptional kunowanzotsanangurwa kuburikidza nepfungwa yemaoperon, akadai selac operon muEscherichia coli. Mulac operon, kuvapo kwelactose kunoita kuti repressor isashande, zvichiita kuti majini anogadzira lactose anyorwe. Uyezve, kuwanikwa kweglucose kunokanganisa protein yeCAP-cAMP, iyo inowedzera transcription kana glucose yakaderera. Muenzaniso uyu unoratidza kuti kudzorwa kwemajini kunogona kubatanidza zviratidzo zvakawanda zvezvakatipoteredza panguva imwe chete.
Kugadziriswa kweRNA mushure mekunyora: kusanganisa uye kusiyana kwechigadzirwa chemajini
MuEukaryotes, RNA ichangobva kunyorwa (pre-mRNA) inofanira kugadziriswa isati yasvika pakukura kwemRNA. Maitiro aya anosanganisira kuwedzerwa chivharo che 5', polyadenylation pamucheto we 3' (poly-A tail), uye kusunganidzwa kubvisa ma introns uye kubatana nema exons. Kurongeka padanho rino kunogona kuchinja mhando yeprotein inogadzirwa kubva kugene rimwe chete.
Imwe nzira yakakosha ndeye alternative splicing, umo musanganiswa wakasiyana wemaexons unosunganidzwa pamwe chete kuti ugadzire mapuroteni isoform akasiyana. Alternative splicing inobvumira kusiyana kukuru kwemapuroteni pasina kuwedzera huwandu hwemajini. Kurongeka kwesplicing kunodzorwa nemapuroteni anosunga RNA uye zviratidzo pa pre-mRNA. Mapatani esplicing anogona kusiyana mumatishu akasiyana, zvichibvumira jini rimwe chete kugadzira chigadzirwa chine basa rakati rematishu iwayo.
Kugadzikana uye kutakurwa kwemRNA: kudzora "hupenyu" hwemashoko ezvemajini
Kana mRNA yakura yaumbwa, masero anogona kudzora kuti inogara kwenguva yakareba sei isati yaora. Kugadzikana kwemRNA kunosarudza kuti mapuroteni akawanda sei anogona kugadzirwa kubva mairi. Dzimwe nzvimbo dzemRNA, kunyanya nzvimbo isina kushandurirwa ye3' (3' UTR), dzine zvinhu zvinosunga mapuroteni anotonga kana maRNA madiki, zvichikanganisa kuora uye kushanda zvakanaka kwekushandura.
Pamusoro pezvo, mRNA inofanira kutakurwa kubva kunucleus kuenda ku cytoplasm. Mune zvimwe zviitiko, mRNA "inotungamirwa" kunzvimbo dzakatarwa mukati mesero (semuenzaniso, mumasero etsinga, kune madendrites kana ma axons). Kuwanikwa kwemRNA kunobvumira kugadzirwa kweprotein pedyo nenzvimbo yayo, zvichiwedzera kushanda zvakanaka uye kururama kwemhinduro dzemasero.
Kupindirana kweRNA neRNA kusina kukodha
Haasi maitiro ese ekudzora magene anotsamira pamapuroteni. MaRNA asina makodhi, akadai sema microRNA (miRNAs) uye ma small interferents RNAs (siRNAs), ndiwo akakosha muzvinhu zvipenyu zvakawanda. ma miRNA anogona kusungana kuti arwise mRNAs uye kudzivirira kushandurwa kana kukurumidzisa kuora kwawo. Iyi nzira, inozivikanwa se RNA interference (RNAi), ine basa guru mukudzora kukura, kudzivirira mavhairasi, uye kugadzikana kwema genome.
Mamwe maRNA asina makodhi, akadai semaRNA marefu asina makodhi (lncRNAs), anogona kukanganisa kuratidzwa kwemajini nenzira dzakasiyana-siyana - kubva pakutungamira chromatin modification complexes kusvika kunzvimbo dzakatarwa kusvika pakushanda se "sponges" dzinosunga miRNAs kuitira kuti dzisakwanise kudzivirira ma mRNA anotarisirwa.
Mutemo wekushandura uye wepashure pekushandura: kudzora padanho reprotein
Kunyangwe kana mRNA iripo, masero anogona kuramba achidzora kunyangwe ikashandurwa kuita mapuroteni. Kudzora kushandurwa kwakakosha kana masero achida mhinduro nekukurumidza, senge kana ari pasi pekumanikidzwa. Zvinhu zvinotanga kushandurwa zvinogona kuvhurwa kana kudziviswa, zvichiwedzera kana kuderedza kugadzirwa kwemapuroteni chaiwo.
Mushure mekunge puroteni yagadzirwa, kudzorwa kwemasero mushure mekushandurwa kunoramba kuchienderera mberi, kusanganisira kupetwa, kupatsanurwa, kuwedzerwa kwemapoka emakemikari (akadai sephosphorylation, glycosylation, ubiquitination), uye kudzorwa kwenzvimbo yayo mukati mesero. Kudzorwa kwemasero kunowanzo ratidza mapuroteni ekuparadzwa neproteasome. Nenzira iyi, masero anogona kudzora mazinga emapuroteni zvakanyanya, kubvisa mapuroteni akakuvara, kana kukurumidza kumisa masaini.
Kubatanidzwa kwezviratidzo uye kukosha kwekutonga kwekutaura kwemajini
Muzvinhu zvipenyu, zvese zviri pamusoro apa zvinoshanda nenzira yakabatana. Semuenzaniso, mahormone esteroid anogona kupinda mumasero uye kusunga kune mareceptor anoshanda sezvinhu zvinoshandura masero. Mareceptor aya anobva atora ma coactivators anoshandura histones kuti avhure chromatin, zvichiwedzera kunyorwa kwemajini anotarisirwa. MRNA inobuda inogona kupatsanurwa zvichienderana nerudzi rwesero, uye yozoshandurwa nekushanda kwakasiyana zvichienderana nemamiriro emuviri.
Kudzora kuratidzwa kwemajini ndiko kunonyanya kukosha pakuchinja kwezvipenyu kuti zvienderane nenzvimbo yazvo. Muzvipembenene, shanduko mukugadzirwa kwemajini dzinozvibvumira kurarama nekuchinja kwekupisa, pH, kana kuwanikwa kwezvinovaka muviri. Muzvirimwa, kudzora majini kunobatsira kupindura kusanaya kwemvura, munyu, uye kurwiswa kwezvirwere. Mumhuka, masoja ekudzivirira muviri anovimba nekutonga kwekugadzirwa kwemajini kuti ashandise majini e cytokines, antibodies, uye mamwe mamorekuru ekudzivirira nekukurumidza asi kwakadzorwa.
Penutup
Kudzora kutaurwa kwemajini muzvinhu zvipenyu inzira yakaoma inobvumira genome imwe chete kugadzira marudzi akasiyana-siyana emasero uye mhinduro dzemuviri. Nekudzora kuwanikwa kweDNA, kudzora kunyorwa kwezvinyorwa, kugadzirisa nekusarudza RNA, kudzora kushandurwa, uye kuona magumo emapuroteni, masero anokwanisa kuchinjika kuzvinodiwa zvemukati uye shanduko dzenharaunda. Kunzwisisa kudzorwa kwekutaura kwemajini hakuna kukosha chete kune biology yekutanga asiwo kunoisa hwaro hwekuvandudzwa kwemishonga yemazuva ano yakadai semishonga yakavakirwa pa epigenetic, kurapa kwemajini, uye kupindira kwakavakirwa paRNA. Sezvo matekinoroji e genomics uye system biology achifambira mberi, kutsvagurudza kudzorwa kwekutaura kwemajini kuchawedzera kuratidza ruzivo rwekuti zvipenyu zvinokura sei, zvinochinjika, uye zvinochengetedza hutano hwazvo.
