microRNAs: Kev nkag siab tshiab ntawm Mechanism of Action in Viral Infections thiab nws qhov tseem ceeb

MicroRNAs lossis luv luv miRNAs (tsis yog yuav tsum tsis meej pem nrog mRNA lossis tus xa xov RNA) tau tshawb pom hauv xyoo 1993 thiab tau kawm ntau yam hauv ob xyoo dhau los lossis yog li ntawd rau lawv lub luag haujlwm hauv kev tswj cov noob qhia. miRNAs qhia txawv nyob rau hauv ntau lub cev hlwb thiab cov ntaub so ntswg. Kev tshawb fawb tsis ntev los no los ntawm cov kws tshawb fawb ntawm Queen's University, Belfast tau nthuav tawm lub luag haujlwm ntawm miRNAs hauv kev tiv thaiv kab mob thaum lub cev hlwb raug cuam tshuam los ntawm cov kab mob. Cov kev tshawb pom no yuav ua rau muaj kev nkag siab zoo dua ntawm tus kab mob thiab lawv cov kev siv los ua lub hom phiaj rau kev txhim kho kho tshiab.  

MicroRNAs los yog miRNAs tau txais koob meej nyob rau ob xyoo dhau los rau lawv lub luag haujlwm hauv cov txheej txheem tom qab kev hloov pauv xws li kev sib txawv, metabolic homeostasis, proliferation thiab apoptosis. ^(1-5). miRNAs me me ib leeg-stranded RNA cov kab ke uas tsis encode rau ib qho proteins. Lawv yog muab los ntawm cov precursors loj, uas yog ob-stranded RNAs. Lub biogenesis ntawm miRNA pib nyob rau hauv lub nucleus ntawm lub cell thiab koom nrog tiam thawj miRNA cov ntawv sau los ntawm RNA polymerase II ua raws li trimming ntawm thawj cov ntaub ntawv sau tseg kom tso cov pre-miRNA hairpin los ntawm ib qho enzyme complex. Qhov tseem ceeb miRNA Tom qab ntawd raug xa mus rau cytoplasm qhov twg nws tau ua los ntawm DICER (ib qho protein ntau uas ntxiv cleaves pre-miRNA), yog li tsim cov mRNA ib leeg-stranded mature. Cov miRNA paub tab ua ke nws tus kheej ua ib feem ntawm RNA induced silencing complex (RISC) thiab induces post-transcriptional gene silencing by fastening RISC to the complementary regions, found in the 3'untranslated regions (UTRs), in the target mRNAs. 

Zaj dab neeg pib hauv 1993 nrog kev tshawb pom ntawm miRNAs in C. elegans los ntawm Lee thiab nws cov npoj yaig ⁽⁶⁾. Nws tau pom tias LIN-14 cov protein raug txo qis los ntawm lwm cov noob caj noob ces hu ua lin-4 thiab qhov kev txo qis no yog qhov tsim nyog rau kev loj hlob larval nyob rau hauv. C. elegans nyob rau theem L1 txog L2. Cov ntawv sau lin-4 tau ua rau txo qis LIN-14 qhia los ntawm kev sib txuas ntxiv rau thaj tsam 3'UTR ntawm lin-4 mRNA, nrog me ntsis kev hloov rau mRNA qib lin-4. Qhov tshwm sim no tau pib xav tias yog tshwj xeeb thiab tshwj xeeb rau C. Elegans, mus txog rau 2000, thaum lawv tau pom nyob rau hauv lwm hom tsiaj ⁽⁷⁾. Txij thaum ntawd los, tau muaj qhov dej nyab ntawm cov ntawv tshawb fawb piav qhia txog kev tshawb pom thiab muaj nyob ntawm miRNAs hauv cov nroj tsuag thiab tsiaj txhu. Ntau tshaj 25000 miRNAs tau tshawb pom txog tam sim no thiab rau ntau tus, lub luag haujlwm tseem ceeb uas lawv ua hauv biology ntawm cov kab mob tseem nyob tsis tau. 

miRNAs exert lawv cov teebmeem los ntawm post-transcriptionally repressing lub mRNAs los ntawm khi rau complementary sites nyob rau hauv lub 3 'UTRs ntawm mRNA lawv tswj. Ib qho kev sib txuam muaj zog ua rau mRNA rau degradation thaum lub zog ua kom tsis muaj zog tsis ua rau muaj kev hloov pauv hauv mRNA qib tab sis ua rau inhibition ntawm kev txhais lus. Txawm hais tias lub luag haujlwm tseem ceeb ntawm miRNA yog nyob rau hauv kev tawm tsam kev tawm tsam, lawv kuj ua raws li cov activators nyob rau hauv tsawg zaus. ⁽⁸⁾. miRNAs ua lub luag haujlwm tseem ceeb hauv lub cev txoj kev loj hlob los ntawm kev tswj cov noob thiab cov khoom lag luam ntawm lub embryonic lub xeev mus rau kev loj hlob ntawm lub cev thiab lub cev. ^(9-11). Ntxiv rau lawv lub luag haujlwm hauv kev tswj hwm cellular homeostasis, miRNAs kuj tau cuam tshuam rau ntau yam kab mob xws li mob qog noj ntshav (miRNAs ua raws li ob qho tib si activators thiab repressor ntawm cov noob), cov kab mob neurodegenerative thiab kab mob plawv. Kev nkag siab thiab piav qhia lawv lub luag haujlwm hauv ntau yam kab mob tuaj yeem ua rau muaj kev tshawb pom biomarker tshiab nrog cov txheej txheem kho tshiab rau kev tiv thaiv kab mob. miRNAs kuj tseem ua lub luag haujlwm tseem ceeb hauv kev txhim kho thiab kev tsim cov kab mob ntawm cov kab mob uas tshwm sim los ntawm cov kab mob microorganisms xws li cov kab mob thiab cov kab mob los ntawm kev tswj cov noob ntawm lub cev tiv thaiv kab mob txhawm rau txhim kho cov lus teb zoo rau tus kab mob. Nyob rau hauv cov ntaub ntawv ntawm tus kab mob kis, Hom I interferons (IFN alpha thiab IFN beta) raug tso tawm raws li cov tshuaj tiv thaiv kab mob cytokines uas tig los hloov lub cev tiv thaiv kab mob txhawm rau txhim kho cov lus teb. ⁽¹²). Kev tsim cov interferons yog nruj tswj hwm ob qho tib si ntawm qib kev sau thiab txhais lus thiab ua lub luag haujlwm tseem ceeb hauv kev txiav txim siab cov lus teb los ntawm tus tswv tsev. Txawm li cas los xij, cov kab mob tau hloov zuj zus txaus los dag ntxias cov tswv tsev hauv kev tiv thaiv lub cev tiv thaiv kab mob no, muab txiaj ntsig zoo rau tus kab mob rau nws qhov kev rov ua dua thiab yog li ua rau cov tsos mob hnyav dua. ^{(12, 13)}. Kev tswj nruj ntawm kev sib cuam tshuam ntawm IFN tsim los ntawm tus tswv tsev thaum kis tus kab mob thiab nws qhov kev tawm tsam los ntawm tus kab mob kis tau txiav txim siab txog qhov twg thiab lub sijhawm ntawm tus kab mob tshwm sim los ntawm tus kab mob no hauv nqe lus nug. Txawm hais tias kev tswj hwm ntawm IFN ntau lawm thiab muaj feem xyuam nrog IFN stimulated genes (ISGs) tau tsim zoo. ⁽¹⁴⁾, lub mechanism ntawm kev txhais lus tswj tau tseem nyob elusive ⁽¹⁵⁾. 

Cov kev tshawb fawb tsis ntev los no los ntawm cov kws tshawb fawb ntawm McGill University, Canada thiab Queens University, Belfast muab kev nkag siab zoo txog kev tswj hwm kev txhais lus IFN ntau lawm uas hais txog lub luag hauj lwm ntawm 4EHP protein nyob rau hauv suppressing IFN-beta ntau lawm thiab kev koom tes ntawm miRNA, miR-34a. 4EHP downregulates IFN ntau lawm los ntawm modulating miR-34a-induced translational silencing ntawm Ifnb1 mRNA. Kev kis tus kab mob RNA thiab IFN beta induction nce qib ntawm miR-34a miRNA, ua rau muaj kev tawm tswv yim tsis zoo ntawm kev tswj xyuas lub voj uas ua rau IFN beta qhia ntawm 4EHP ⁽¹⁶⁾. Txoj kev tshawb no tseem ceeb heev nyob rau hauv lub wake ntawm tus kab mob kis tau tshwm sim tam sim no Covid-19 (ib qho kab mob tshwm sim los ntawm tus kab mob RNA) vim nws yuav pab kom nkag siab txog tus kab mob ntxiv thiab ua rau muaj txoj hauv kev tshiab los daws tus kab mob los ntawm kev hloov kho cov theem ntawm miR-34a miRNA siv tus tsim tawm activators / inhibitors thiab sim lawv hauv kev sim tshuaj rau nws cov teebmeem ntawm IFN teb. Muaj cov ntaub ntawv qhia txog kev sim tshuaj siv IFN beta therapy ⁽¹⁷⁾ thiab txoj kev tshawb no yuav pab tshem tawm cov txheej txheem molecular los ntawm kev qhia txog lub luag haujlwm ntawm miRNA hauv kev tswj hwm tus tswv tsev txhais lus rau kev tswj hwm ib puag ncig homeostatic. 

Kev tshawb nrhiav yav tom ntej thiab kev tshawb fawb txog qhov no thiab lwm yam paub thiab tshwm sim miRNAs Ua ke nrog kev koom ua ke ntawm cov kev tshawb pom no nrog cov ntaub ntawv genomic, transcriptomic, thiab / lossis cov ntaub ntawv proteomic, yuav tsis tsuas yog txhim kho peb cov kev nkag siab txog kev sib cuam tshuam ntawm tes thiab kab mob, tab sis kuj yuav ua rau cov tshiab. miRNA raws li kev kho mob los ntawm kev siv miRNA ua actimirs (siv miRNAs ua activators hloov miRNAs uas tau hloov pauv lossis tshem tawm) thiab antagomirs (siv miRNAs ua antagonists qhov twg muaj qhov txawv txav ntawm qhov hais tias mRNA) rau kev nthuav dav thiab tshwm sim ntawm tib neeg thiab tsiaj cov kab mob.  

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