澳大利亞國(guó)立大學(xué)醫(yī)學(xué)研究所,，化學(xué)研究所的科學(xué)家發(fā)現(xiàn)新的免疫理論,，相關(guān)成果公布在最新一期的Immunity上,，并列為封面文章,。
眾所周知,，B細(xì)胞具有記憶性,，一般來說B細(xì)胞的記憶性的形成與DNA序列的改變有聯(lián)系，B細(xì)胞通過改變DNA序列來維持細(xì)胞的記憶性,。但是,，免疫細(xì)胞的記憶性機(jī)制研究比較多的是B細(xì)胞，相比之下,，T細(xì)胞研究的比較少,。
研究小組發(fā)現(xiàn)，記憶性T細(xì)胞的分化過程中,， RNA重排起重要作用,。研究小組以小鼠的研究模型，通過沉默一個(gè)記憶性T細(xì)胞分化的關(guān)鍵基因ptprc（是產(chǎn)生記憶性T細(xì)胞CD45RO的重要基因）,，結(jié)果發(fā)現(xiàn)記憶性T細(xì)胞的比例發(fā)生改變,。并且RNA結(jié)合蛋白hnRNALL發(fā)生改變,，會(huì)導(dǎo)致RNA的識(shí)別區(qū)域變得不穩(wěn)定。
研究者發(fā)現(xiàn)hnrpll突變會(huì)導(dǎo)致T細(xì)胞不在外周淋巴結(jié)聚集,，但不影響增殖,。對(duì)這些突變細(xì)胞進(jìn)行外顯子檢測(cè)分析，結(jié)果發(fā)現(xiàn)記憶性T細(xì)胞的mRNA接過程發(fā)生的廣泛的改變,。并且相同的變化還出現(xiàn)在神經(jīng)組織中,，這可能是引發(fā)記憶性T細(xì)胞發(fā)生變化的原因。（生物谷Bioon.com）
生物谷推薦原始出處：
Immunity,19 December 2008 doi:10.1016/j.immuni.2008.11.004
Memory T Cell RNA Rearrangement Programmed by Heterogeneous Nuclear Ribonucleoprotein hnRNPLL
Zuopeng Wu1,Xinying Jia2,Laura de la Cruz2,Xun-Cheng Su2,Bruz Marzolf3,Pamela Troisch3,Daniel Zak3,Adam Hamilton1,Belinda Whittle1,Di Yu1,Daniel Sheahan1,Edward Bertram1,Alan Aderem3,Gottfried Otting2,Christopher C. Goodnow1,4,,andGerard F. Hoyne1,4
1 John Curtin School of Medical Research, Australian Phenomics Facility, Australian National University, Canberra ACT 0200, Australia
2 Research School of Chemistry, Australian National University, Canberra ACT 0200, Australia
3 Institute for Systems Biology, 1441 North 34th St., Seattle, WA 98103-9804, USA
Corresponding author
4 These authors contributed equally
Summary
Differentiation of memory cells involves DNA-sequence changes in B lymphocytes but is less clearly defined in Tcells. RNA rearrangement is identified here as a key event in memory Tcell differentiation by analysis of a mouse mutation that altered the proportions of naive and memory Tcells and crippled the process of Ptprc exon silencing needed to generate CD45RO in memory Tcells. A single substitution ina memory-induced RNA-binding protein, hnRNPLL, destabilized an RNA-recognition domain that bound with micromolar affinity to RNA containing the Ptprc exon-silencing sequence. Hnrpll mutation selectively diminished Tcell accumulation in peripheral lymphoid tissues but not proliferation. Exon-array analysis of Hnrpll mutant naive and memory Tcells revealed an extensive program of alternative mRNA splicing in memory Tcells, coordinated by hnRNPLL. A remarkable overlap with alternative splicing in neural tissues may reflect a co-opted strategy for diversifying memory Tcells.
