約翰霍普金斯醫(yī)學(xué)院的研究人員發(fā)現(xiàn)一種與眾不同的microRNAs，這種microRNAs在其內(nèi)部組件的帶領(lǐng)下遷移到細(xì)胞核中,。研究結(jié)果刊載于1月5日的Science中,。
MicroRNAs在癌癥和正常發(fā)育過程中,，都發(fā)揮著重要的功能，microRNA可以附著,、破壞攜帶蛋白編碼序列的長鏈RNA,，這也是MicroRNAs常出現(xiàn)在核糖體附近的原因。
Joshua Mendell率領(lǐng)的研究小組針對(duì)200多個(gè)已知的人類MicroRNAs進(jìn)行分析調(diào)查時(shí),，發(fā)現(xiàn)一種與眾不同的MicroRNA,。
文章第一作者Hun-Way Hwang表示，這種MicroRNA出現(xiàn)的時(shí)間和出現(xiàn)的地點(diǎn)與預(yù)期的不同,。MicroRNA通常由20－25個(gè)核苷酸構(gòu)成,，Mendell小組發(fā)現(xiàn)這種奇特的miR-29b末端的6個(gè)核苷酸序列，與其它 microRNA的末端明顯不同,，能夠控制 microRNA在細(xì)胞中的定位,。
研究人員將這六個(gè)核苷酸從miR-29b上剪切下來,，連接到另一種microRNA上，結(jié)果新的microRNA與 miR-29b一樣,，會(huì)遠(yuǎn)離細(xì)胞蛋白質(zhì)工廠而進(jìn)入細(xì)胞核,，將六個(gè)核苷酸連接在siRNA上，結(jié)果新的siRNA也會(huì)進(jìn)入細(xì)胞核,。
這些研究結(jié)果說明microRNAs雖然微小,，但是其含有的短鏈核苷酸序列能夠控制它們?cè)诩?xì)胞中的行為。Mendell希望利用在miR-29b中發(fā)現(xiàn)的細(xì)胞郵政編碼,，將其它microRNAs 和 siRNAs帶入細(xì)胞核,，以關(guān)閉特殊位置的基因。
由于microRNAs在癌癥和正常的發(fā)育中有重要意義,，所以研究人員希望針對(duì)miR-29b進(jìn)一步研究,，以發(fā)現(xiàn)microRNAs的更多功能。
英文原文：
Renegade RNA -- Clues to cancer and normal growth
Researchers at Johns Hopkins have discovered that a tiny piece of genetic code apparently goes where no bit of it has gone before, and it gets there under its own internal code.
A report on the renegade ribonucleic acid, and the code that directs its movement, will be published Jan. 5 in Science.
MicroRNAs, already implicated in cancer and normal development, latch on to and gum up larger strands of RNA that carry instructions for making the proteins that do all the cell's work. They are, says Joshua Mendell, M.D., Ph.D., an assistant professor in the McKusick-Nathans Institute of Genetic Medicine at Hopkins, like "molecular rheostats that fine-tune how much protein is being made from each gene."
That's why normally microRNAs always have appeared to stick close to the cell's protein-making machinery.
But during a survey of more than 200 of the 500 known microRNAs found in human cells, Mendell's team discovered one lone microRNA "miles away" --- in cellular terms --- from all the others.
"It was so clearly in the wrong place at the wrong time for what we thought it was supposed to be doing that we just had to figure out why," says Hun-Way Hwang, a graduate student in human genetics and contributor to the study.
Consisting of only 20 to 25 nucleotide building blocks (compared to other types of RNA that can be thousands of nucleotides long), each microRNA has a different combination of blocks. Mendell's team realized that six building blocks at the end of the wayward miR-29b microRNA were noticeably different from the ends of other microRNAs.
Suspicious that the six-block end might have something to do with miR-29b's location, the researchers chopped them off and stuck them on the end of another microRNA. When put into cells, the new microRNA behaved just like miR-29b, wandering far away from the cell's protein-making machinery and into the nucleus, where the cell's genetic material is kept.
The researchers then stuck the same six-block end onto another type of small RNA, a small-interfering RNA or siRNA that turns off genes. This also forced the siRNA into the nucleus.
According to Mendell, these results demonstrate for the first time that despite their tiny size, microRNAs contain elements consisting of short stretches of nucleotide building blocks that can control their behavior in a cell. Mendell hopes to take advantage of the built-in "cellular zip code" discovered in miR-29b as an experimental tool. For example, he plans to force other microRNAs and siRNAs into the nucleus to turn off specific sets of genes.
Mendell's team is actively hunting for additional hidden microRNA elements that control other aspects of their behavior in cells. They also are curious to figure out what miR-29b is doing in the nucleus. Because microRNAs have been implicated in cancer as well as normal development, Mendell hopes that further study of miR-29b will reveal other, hidden functions of microRNAs.
