據(jù)悉,，一個(gè)人的全部DNA中高達(dá)95％的DNA被認(rèn)為是垃圾DNA。為了防止這些進(jìn)化過程中產(chǎn)生的廢物重排染色體并導(dǎo)致疾病,，現(xiàn)代染色體生物學(xué)理論認(rèn)為,，必然存在一些能夠使它們沉默的天然機(jī)制。
RNA沉默機(jī)制能通過破壞攜帶DNA指令的mRNA分子來使基因表達(dá)沉默,。兩年前,，有研究表明RNA沉默機(jī)器在形成異染色質(zhì)——無轉(zhuǎn)錄活性的非活動(dòng)染色質(zhì)——的過程中是必需的，這也暗示出生物學(xué)中存在的新“規(guī)則”,。但Texas A&M大學(xué)和Oregon大學(xué)的研究人員卻持不同意見,。在發(fā)表在最新一期Science上的文章中，他們打破了以往的“規(guī)則”,。
Texas A&M 大學(xué)生物學(xué)副教授Rodolfo Aramayo認(rèn)為,，該研究將有助于人們對(duì)染色體結(jié)構(gòu)復(fù)雜性的理解，進(jìn)而在基因治療中發(fā)揮重要作用,。由于大部分先天缺陷是由染色體異常造成的,，因此了解染色體的機(jī)構(gòu)及其如何運(yùn)作將非常重要。
在對(duì)脈胞菌（Neurospora crassa）的一項(xiàng)研究中,，Rodolfo Aramayo及其同事構(gòu)建出一種突變的細(xì)胞,，這種細(xì)胞不能制造出RNA沉默機(jī)制所需的關(guān)鍵成份，結(jié)果他們發(fā)現(xiàn)這種細(xì)胞的異染色質(zhì)能正常形成,。
Aramayo說,，“我們可以將染色體想象成一條高速路，為了正常運(yùn)行,，高速路的一些區(qū)段需要照明,，也就是說DNA必須被表達(dá)；而其它區(qū)段則不需要照明,，即DNA不需要表達(dá),，或這些區(qū)段必須被異染色質(zhì)化。......有一些士兵負(fù)責(zé)關(guān)掉高速路上的某些燈,。依據(jù)這個(gè)規(guī)則,，所有人都認(rèn)為這些‘士兵’就是RNA沉默機(jī)器。但我們的研究表明,，當(dāng)我們?nèi)サ暨@些沉默機(jī)器的‘士兵’時(shí),，還有其它‘人’仍然能將燈關(guān)掉！我們不知道這個(gè)‘關(guān)燈人’到底是誰,，但我們正在努力找出他,。”
研究表明，細(xì)胞在進(jìn)化過程中會(huì)產(chǎn)生出多種不同的通路去完成同一工作,。這一點(diǎn)非常重要,，因?yàn)槿祟惣?xì)胞也可能有相似的機(jī)制,。
進(jìn)一步掌握染色體生物學(xué)的細(xì)節(jié)是進(jìn)行基因治療的基礎(chǔ)。Aramayo說,，“了解正常的染色體生物學(xué)并非一時(shí)好奇,，而是戰(zhàn)勝疾病必須作的事情......不了解染色體的工作原理，我們永遠(yuǎn)不能實(shí)現(xiàn)基因療法,。希望在將來我們能通過引入基因來糾正遺傳錯(cuò)誤,，從而幫助人們戰(zhàn)勝疾病。”他又補(bǔ)充說,，“即使我們進(jìn)行的是基礎(chǔ)性的研究，但對(duì)整個(gè)社會(huì)的意義是重大的,。”
Function and properties of silencing suppressor proteins
Researchers look into components of RNA silencing machinery
COLLEGE STATION, July 27, 2004 - Up to 95 percent of a person's DNA is believed to be junk DNA. In order to prevent these relics of evolution from rearranging chromosomes and causing disease, natural mechanisms exist to silence them, according to contemporary theories of chromosome biology.
The RNA silencing machinery silences gene expression, by destroying RNA, a molecule that carries out DNA's instructions. Two years ago, components of the RNA silencing machinery were shown to be absolutely required for forming heterochromatin, a chromatin state that silences DNA, suggesting a new rule in biology. But researchers from Texas A&M University and the University of Oregon disagree.
They broke that rule in reporting their findings in the July 25 issue of Science magazine. Funding for the research is supported by grants from the National Institutes of Health.
Knowledge gained from their research will enable scientists to better understand the complexities of chromosome biology, which ultimately will lead to conquering disease by the means of gene therapy, says Rodolfo Aramayo, associate professor of biology at Texas A&M University, who specializes in genetics and studies the biology of meiotic chromosomes. Since the majority of birth defects are caused by chromosomal abnormalities, he says it is absolutely fundamental to understand how chromosomes work.
"Understanding normal chromosome biology is more than a curious scientific endeavor," says Aramayo. "It is a must if we ever are to conquer disease."
In a study with Neurospora crassa, a mold, Aramayo and his colleagues created mutant cells that cannot produce any key components of the RNA silencing mechanism, and discovered that heterochromatin formed just fine.
"Think about a chromosome as being a highway," says Aramayo. "In order to function properly, some sections of the highway must have illumination, which means DNA must be expressed, whereas other sections must not have illumination, which means DNA must not be expressed, or that the region must be heterochromatic.
"Some soldiers carry the duty of turning off certain lights along the highway. Everybody thought these soldiers belong to the RNA silencing machinery, as the rule says. But what our research has shown is that, when we killed these RNA silencing machinery soldiers, someone else is still turning the lights off! We don't know who did it, but we're on our way to find out."
"What we have shown," Aramayo says, "is that cells have evolved more than one way to do the same thing. And this is important, because similar mechanisms might be present in human cells."
In regard to the growing knowledge base in understanding chromosome biology for doing gene therapy, Aramayo says, "Without understanding how chromosomes work, we will never be able to perform gene therapy. Hopefully in the future, we are going to be able to correct genetic mistakes by introducing genes and help people overcome these problems."
Aramayo adds, "Even though we are doing basic research, the implications for society in general are broad."
