I-microRNAs: Ukuqonda okutsha kweNdlela yokuSebenza kwiNtsholongwane yeNtsholongwane kunye noBaluko bayo

IiMicroRNA okanye kwii-miRNA ezimfutshane (ezingadideki ne-mRNA okanye i-RNA yesithunywa) zafunyanwa ngo-1993 kwaye ziye zafundwa ngokubanzi kwiminyaka engamashumi amabini edlulileyo okanye kunjalo ngendima yazo yokulawula ukubonakaliswa kwemfuza. Ii-miRNAs zibonakaliswa ngokwahlukileyo kwiiseli ezahlukeneyo zomzimba kunye nezicubu. Uphando lwakutsha nje olwenziwe zizazinzulu kwiYunivesithi yaseQueen, iBelfast iveze indima yobuchwephesha ye-miRNAs kulawulo lwamajoni omzimba xa iiseli zomzimba zicelwa umngeni ziintsholongwane. Ezi ziphumo ziya kukhokelela ekuqondweni okuphuculweyo kwesi sifo kunye nokusetyenziswa kwazo njengeenjongo zophuhliso lonyango olululo.  

MicroRNAs okanye miRNAs baye bafumana ukuthandwa kwisithuba seminyaka engamashumi amabini edlulileyo ngendima yabo kwiinkqubo zokukhuphela emva kokubhaliweyo ezifana nokwahlula, i-homeostasis ye-metabolic, ukwanda kunye ne-apoptosis. ^(1-5). miRNAs zincinci zinemisonto enye RNA Ulandelelwano olungafaki iikhowudi kuzo naziphi na iiproteni. Zivela kwii-precursors ezinkulu, eziphindwe kabini Ii-RNAs. I-biogenesis ye I-miRNA iqala kwinucleus yeseli kwaye ibandakanya isizukulwana sokuqala I-miRNA imibhalo nge RNA i-polymerase II ilandelwa kukuchetywa kwe-primary transcript ukukhulula i-pre-miRNA hairpin nge-enzyme complex. Eyokuqala I-miRNA Ithi ke ithunyelwe ngaphandle kwicytoplasm apho isetyenziswa yi-DICER (iprotein complex ephinda icande i-pre-miRNA), ngokwenza oko ivelise i-miRNA ene-single-stranded miRNA. I-miRNA evuthiweyo idibanisa ngokwayo njengenxalenye ye-RNA i-silence complex (RISC) kwaye ibangela ukuthuliswa kofuzo lwe-post-transcriptal ngokuqinisa i-RISC kwimimandla ehambelanayo, efunyenwe ngaphakathi kwe-3 'imimandla engaguqulelwanga (UTRs), kwi-mRNAs ekujoliswe kuyo. 

Ibali laqala ngo-1993 ngokufunyanwa kwe miRNAs in C. ii-elegans nguLee nabalingane bakhe ⁽⁶⁾. Kwaphawulwa ukuba iprotheni ye-LIN-14 yathotywa ngomnye ujini obhaliweyo obizwa ngokuba yi-lin-4 kwaye oku kuncipha kwakuyimfuneko kuphuhliso lombungu C. ii-elegans ekuqhubeleni phambili ukusuka kwinqanaba L1 ukuya kwi-L2. I-lin-4 ekhutshelweyo ibangele ukuthotywa kwe-LIN-14 intetho ngokubophelela okuhambelanayo kwingingqi ye-3'UTR ye-lin-4. mRNA, kunye notshintsho oluncinci kwi mRNA amanqanaba e-lin-4. Esi siganeko ekuqaleni kwakucingelwa ukuba sikhethekile kwaye sithe ngqo C. elegans, de kwaba malunga ne-2000, xa zafunyanwa kwezinye iintlobo zezilwanyana ⁽⁷⁾. Ukusukela ngoko, kuye kwakho umkhukula wamanqaku ophando achaza ukufunyanwa kunye nobukho be-miRNAs kuzo zombini izityalo kunye nezilwanyana. Ngaphezulu kwe25000 miRNAs zifunyenwe ukuza kuthi ga ngoku kwaye kwabaninzi, eyona ndima bayidlalayo kwibhayoloji yezinto eziphilayo kusenzima. 

miRNAs basebenzise iziphumo zabo ngokucinezela i-mRNAs emva kokubhala ngokuzibophelela kwiindawo ezincedisayo kwi-3' UTRs ye-mRNA abayilawulayo. Ukuhambelana okuqinileyo kuphawula i-mRNA yokuthotywa ngelixa ukuhambelana okubuthathaka kungabangeli naluphi na utshintsho kumanqanaba e-mRNA kodwa kubangela uthintelo loguqulo. Nangona indima enkulu ye-miRNA ikuxinzelelo lokubhaliweyo, zikwasebenza njengabavuseleli kwiimeko ezinqabileyo. ⁽⁸⁾. Ii-miRNAs zidlala indima ebaluleke kakhulu kuphuhliso lwento ephilayo ngokulawula imizila yemfuza kunye nemveliso yemfuza ukusuka kwimeko ye-embryonic ukuya kuphuhliso lwamalungu kunye neenkqubo zamalungu. ^(9-11). Ukongeza kwindima yabo ekugcineni i-homeostasis yeselula, ii-miRNAs ziye zabandakanyeka kwizifo ezahlukeneyo ezinjengomhlaza.miRNAs zisebenza njengazo zombini ii-activators kunye ne-repressor of genes), ukuphazamiseka kwe-neurodeergenerative kunye nezifo zentliziyo. Ukuqonda kunye nokucacisa indima yabo kwizifo ezahlukeneyo kunokukhokelela ekufumaneni i-biomarker entsha kunye neendlela ezintsha zonyango zokuthintela izifo. miRNAs kwakhona idlala indima ebalulekileyo ekuphuhliseni kunye ne-pathogenesis yosulelo olubangelwa yi-micro-organisms ezifana neebhaktheriya kunye neentsholongwane ngokulawula imfuza ye-immune system ukukhupha impendulo esebenzayo kwisifo. Kwimeko yosulelo lwentsholongwane, Uhlobo lwe-Interferon (i-IFN alpha kunye ne-IFN beta) lukhutshwa njenge-cytokines elwa nentsholongwane, leyo yona imodareyitha amajoni omzimba ukuze akhuphe impendulo yokulwa. ⁽¹²). Ukuveliswa kwe-interferon kulawulwa ngokuqinileyo zombini kwinqanaba lokubhaliweyo kunye nokuguqulelwa kwaye kudlala indima ebalulekileyo ekunqumeni impendulo ye-anti-virus ngumninimzi. Nangona kunjalo, iintsholongwane ziye zavela ngokwaneleyo ukuze zikhohlise iiseli ezibambayo ukuba zicinezele le mpendulo yokuzivikela komzimba, inika ithuba lentsholongwane ngokuphindaphinda kwayo kwaye ngokwenza njalo zandisa iimpawu zesifo. ^{(12, 13)}. Ulawulo oluqinileyo lokusebenzisana phakathi kokuveliswa kwe-IFN ngumninimzi phezu kosulelo lwentsholongwane kunye nokunyanzeliswa kwayo yintsholongwane eyosulelayo inquma ubungakanani kunye nobude besifo esibangelwa yintsholongwane ekhankanywe. Nangona ulawulo olubhaliweyo lwemveliso ye-IFN kunye ne-IFN ehambelana neegenes ezivuselelweyo (ISGs) zisekwe kakuhle. ⁽¹⁴⁾, indlela yokulawula ukuguqulela ihleli inzima ⁽¹⁵⁾. 

Uphononongo lwakutsha nje olwenziwe ngabaphandi kwiYunivesithi yaseMcGill, eCanada nakwi IYunivesithi yaseQueens, IBelfast ibonelela ngobuchule bokuqonda kulawulo loguqulo lwe IFN imveliso ebonisa indima yeprotheni ye-4EHP ekucinezeleni imveliso ye-IFN-beta kunye nokubandakanyeka kwe-miRNA, miR-34a. I-4EHP ilawula imveliso ye-IFN ngokumodareyitha i-miR-34a-induced translational silence ye-Ifnb1 mRNA. Usulelo kunye neentsholongwane ze-RNA kunye nokufakwa kwe-beta ye-IFN kwandisa amanqanaba e-miR-34a miRNA, okubangela ukuba i-loop yokulawula impendulo engalunganga icinezele i-IFN ibonakaliso ye-beta nge-4EHP. ⁽¹⁶⁾. Olu phononongo lubaluleke kakhulu emva kobhubhane okhoyo ngoku obangelwe Covid-19 (usulelo olubangelwa yintsholongwane ye-RNA) njengoko luya kunceda ekuqondeni ngakumbi isifo kwaye lukhokelele kwiindlela ezintsha zokujongana nosulelo ngokumodareyitha amanqanaba e-miR-34a miRNA usebenzisa ii-activators/inhibitors zomyili kunye nokuzivavanya kulingo lwezonyango iziphumo zayo kwimpendulo ye-IFN. Kukho iingxelo zezilingo zeklinikhi ezisebenzisa unyango lwe-beta ye-IFN ⁽¹⁷⁾ kwaye olu phononongo luya kunceda ukutyhila iindlela zemolekyuli ngokuqaqambisa indima ye-miRNA ekulawuleni ngokwangaphakathi oomatshini boguqulo bokugcina ummandla we-homeostatic. 

Uphando lwexesha elizayo kunye nophando ngoko kunye nezinye ezaziwayo nezivelayo miRNAs kudityaniswa nokudityaniswa kwezi zinto zifunyanisiweyo kunye ne-genomic, transcriptomic, kunye/okanye idatha yeproteomic, ayisayi kuphucula nje ukuqonda kwethu ngoomatshini bokusebenzisana kweselula kunye nesifo, kodwa kuya kukhokelela kwinoveli. I-miRNA Unyango olusekwe ngokuxhaphaza i-miRNA njenge actimirs (usebenzisa i-miRNAs njengezivuseleli zokutshintsha indawo miRNAs eziye zatshintshwa okanye zacinywa) kunye nabachasi (ukusebenzisa i-miRNAs njengabachasi apho kukho ukulawulwa okungaqhelekanga kwe-mRNA exeliweyo) kwizifo ezixhaphakileyo nezisakhulayo zabantu nezilwanyana.  

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