[0320]《Cell 》基因控制达到新的水平

阿三

基因控制达到新的水平
--小分子RNA被证实比想象中的更有影响力
人体中可能有超过三分之一的基因是由被称为microRNAs的小分子所调节的。美国科学家的这一见解表明，首次于2000年发现的这类分子可能在从细胞生成到细胞死亡的几乎每一个过程中发挥着作用，它们甚至可以用于治疗人类疾病。
MicroRNAs 有点像DNA片段，由大约22个化学“字母”（核苷酸）组成。它们通过有效地阻碍细胞中基因的正常功能而发挥其作为控制器的作用。MicroRNAs识别并结合到特定的mRNAs上，使后者无法翻译出蛋白质。
David Bartel和他的同事们构建了一种可以快速扫描人类基因mRNAs序列的电脑程序，以期得到那些可能是MicroRNAs的靶序列。他们还核对了这些相同的序列是否也存在于鼠、狗和鸡的相应基因里。如果在其他动物中同样的基因可能由MicroRNAs调节，那么某个基因是由MicroRNA调节的观点将会得到支持。
至少三分之一的基因可能由MicroRNAs调节的，在Cell中该小组对此做了更详细的报告[1]  这个数字比先前的估计多得多，比如去年有一份报告就估计有10%或者更多。
研究组成员Chris Burge说：“因为这只是一个大致的估计，真实的数字可能要更多。”例如，该研究还无法确定那些不存在于其他动物中基因在人类中是否为MicroRNAs所调节。
这一发现还支持了一种观点，那就是当MicroRNAs出错时，可能引发诸如具有癌症特征的失控的细胞分裂等异常情况。
目前认为至少有250种不同的MicroRNAs，而发表在Cell上的另一项新的研究表明可能有200到300种。[2]
MicroRNAs能阻碍细胞中基因正常功能的这一原理已经被研究人员用于使基因“沉默”，此项技术称为RNA干涉或RNAi。

[1]Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets.
Lewis BP, Burge CB, Bartel DP.
We predict regulatory targets of vertebrate microRNAs (miRNAs) by identifying mRNAs with conserved complementarity to the seed (nucleotides 2-7) of the miRNA. An overrepresentation of conserved adenosines flanking the seed complementary sites in mRNAs indicates that primary sequence determinants can supplement base pairing to specify miRNA target recognition. In a four-genome analysis of 3' UTRs, approximately 13,000 regulatory relationships were detected above the estimate of false-positive predictions, thereby implicating as miRNA targets more than 5300 human genes, which represented 30% of our gene set. Targeting was also detected in open reading frames. In sum, well over one third of human genes appear to be conserved miRNA targets.
Cell. 2005 Jan 14;120(1):15-20
[2]Phylogenetic shadowing and computational identification of human microRNA genes.
Berezikov E, Guryev V, van de Belt J, Wienholds E, Plasterk RH, Cuppen E.
We sequenced 122 miRNAs in 10 primate species to reveal conservation characteristics of miRNA genes. Strong conservation is observed in stems of miRNA hairpins and increased variation in loop sequences. Interestingly, a striking drop in conservation was found for sequences immediately flanking the miRNA hairpins. This characteristic profile was employed to predict novel miRNAs using cross-species comparisons. Nine hundred and seventy-six candidate miRNAs were identified by scanning whole-genome human/mouse and human/rat alignments. Most of the novel candidates are conserved also in other vertebrates (dog, cow, chicken, opossum, zebrafish). Northern blot analysis confirmed the expression of mature miRNAs for 16 out of 69 representative candidates. Additional support for the expression of 179 novel candidates can be found in public databases, their presence in gene clusters, and literature that appeared after these predictions were made. Taken together, these results suggest the presence of significantly higher numbers of miRNAs in the human genome than previously estimated.
Cell. 2005 Jan 14;120(1):21-4