A short history of a short RNA.
A short history of a short RNA.
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DOI：
10.1016/s0092-8674(04)00035-2
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发表时间：
2004-01-23
期刊：
影响因子：
64.5
通讯作者：
Ambros, Victor
中科院分区：
文献类型：
--
作者：
Lee, Rosalind;Feinbaum, Rhonda;Ambros, Victor
Horvitz实验室（Ruvkun等人，1989），而加里通过分离突变（e912）继续到20世纪70年代中期。在他自己的MGH实验室中对lin-14（一种新的核蛋白）基因进行了测序。加里的实验室首先由Horvitz和Sulston（1980）描述，并发现n355和n536功能获得性突变由Chalfie等人详细描述。（1981年）。lin-4（e912）是3！非翻译区（UTR）的动物看起来很可怕：它们长成长而细的lin-14 mRNA的“成虫”，而LIN-14蛋白水平与幼虫皮肤一样，并且它们未能在蠕虫非正常阶段的转录后下调时停止蜕皮，从而进入幼虫期外。Chalpingment（Wightman等人，1991年）。因此，如果lin-4 fie et al.（1981）表明，e912雌雄同体，并参与lin-14的时间调节，它的男性是完全缺失的许多细胞类型可能会这样做，通过lin-14 3！UTR。和野生型典型的形态结构尽管lin-成虫之间有有趣的对应关系，但含有许多额外的细胞14和lin-4突变体表型的拷贝，我们并不真正确定通常只在早期幼虫阶段产生。lin-4的克隆和分子鉴定表明e912突变是导致突变失败的原因，这将是一个值得研究的项目，因为lin-4（e912）是lin-4唯一已知的突变等位基因。如果mal，表明lin-4可能编码一个主调节因子lin-4是一个正常的蠕虫基因，我们就知道敲除的基因是发育时间的调控因子。对我们来说，lin-4的一个特别吸引人的特点是它能筛选出产蛋缺陷突变体。e912可能与lin-14有亲缘关系。lin-14被发现不是一个简单的功能丧失突变，在一个规则的埃德温（芯片）弗格森，研究生在鲍勃托利基因。如果e912是一种罕见的《双城之战》基因呢。Chip正在表征以控制C.与正常基因活动无关的线虫？在这种情况下，分子性外阴（Ferguson等人，1987年）。lin-4（e912）她对e912的分析不会告诉我们任何原教旨主义者缺乏的东西，甚至是一个外阴的暗示（由于他们对正常发育的心理。另一方面，未能产生适当指定的外阴precur-一个乐观的观点是，lin-4可能是一个非常小的，或细胞），因此不能产卵（这是传统的，基因。一个基因编码一个因此孵化在他们的母亲和消耗非常短的蛋白质可能会提出一个非常小的目标她）。在培养lin-4（e912）动物进行突变时，奇普偶然发现了功能等位基因，这解释了lin-4缺失遗传实验的稀缺性。我们不记得认为lin-4可能是一个自发的回复突变体，显示几乎正常的编码一个小的调节RNA，直到很久以后，当形态和产卵。奇普认为，我们的数据最终迫使我们考虑这种可能性。负责抑制突变的是以前的一个lin-4克隆项目在维克托的哈佛实验室开始未知基因lin-14。后来，维克托作为博士后工作--在1988年夏天，当一名博士后研究员在Horvitz实验室鉴定出杨贤杰的表观无效等位基因时，他用lin-4区域的RFLP多态性染色体进行了遗传作图实验。仙姐转移到其他追求在.
Horvitz lab (Ruvkun et al., 1989), and Gary went on to mid 1970s through the isolation of a mutation (e912). sequence the lin-14 (a novel nuclear protein) gene in his The remarkable developmental defects of lin-4 (e912) own lab at MGH (Ruvkun and Giusto, 1989). Gary’s lab were first described by Horvitz and Sulston (1980) and discovered that the n355 and n536 gain-of-function mucharacterized in detail by Chalfie et al.(1981). lin-4 (e912) tations are deletions in the 3! untranslated region (UTR) animals look terrible: they grow into long, thin “adults” of the lin-14 mRNA, and that LIN-14 protein level is with a larval skin, and they fail to stop molting at the posttranscriptionally downregulated during worm denormalstageandthusundergoextralarvalstages. Chalvelopment (Wightman et al., 1991). Therefore, if lin-4 fie et al.(1981) showed that e912 hermaphrodites and were involved in the temporal regulation of lin-14, it males are completely missing many of the cell types would probably do so via the lin-14 3! UTR. and morphological structures typical of the wild-type Despite the intriguing correspondence between lin-adults, and instead contain many extra copies of cells14 and lin-4 mutant phenotypes, we were not really sure ordinarily produced only at an early larval stage. It apthat the cloning and molecular characterization of lin-4 peared that the e912 mutation was causing a failure of would be a worthwhile project, because the lin-4 (e912) temporal developmental switches throughout the animutation was the only known mutant allele of lin-4. If mal, indicating that lin-4 might encode a master regula-lin-4 were a normal worm gene, we knew that knockout tor of developmental timing. alleles should have been more easily recovered in For us, a particularly alluring feature of lin-4 was its screens for egg-laying defective mutants. Perhaps e912 genetic relationship with lin-14. lin-14 was discovered was not a simple loss-of-function mutation in a regulaby Edwin (Chip) Ferguson, a graduate student in Bob tory gene. What if e912 were a rare, arcane genetic Horvitz’s lab. Chip was characterizing genetic pathways rearrangement that disturbed development in a fashion controlling steps in development of the C. elegans herunrelated to normal gene activity? In that case, molecumaphrodite vulva (Ferguson et al., 1987). lin-4 (e912) her- lar analysis of e912 would not teach us anything fundamaphrodites lack even a hint of a vulva (owing to their mental about normal development. On the other hand, failure to generate appropriately specified vulva precur- an optimistic view was that lin-4 might be a very small, sor cells) and hence are unable to lay their eggs (which but otherwise conventional, gene. A gene encoding a consequently hatch inside their mother and consume very short protein might present a very small target for her). While growing cultures of lin-4 (e912) animals for mutagenesis, explaining the scarcity of lin-4 loss-ofgenetic experiments, Chip serendipitously discovered function alleles. We do not recall thinking that lin-4 might a spontaneous revertant that displayed nearly normal encode a small regulatory RNA until much later on, when morphology and egg-laying. Chip determined that the our data finally forced us to consider the possibility. responsible suppressor mutation was in a previously The lin-4 cloning project in Victor’s Harvard lab began unknown gene, lin-14. Later, Victor, as a postdoc work- in the summer of 1988, when a postdoctoral fellow, ing in the Horvitz lab, identified apparent null alleles of Xianjie Yang, conducted genetic mapping experiments with chromosomes polymorphic for RFLPs in the lin-4 region. Xianjie shifted to other pursuits at the …