核仁小RNA与肺癌

核仁小RNA（small nucleolar RNA, snoRNA）是一类定位于核仁内的短链非编码RNA,在多种RNA的加工修饰过程中发挥重要作用。随着人们对基因组认识的深入,snoRNA等非编码RNA的结构及功能已成为研究的热点。近年来有研究表明,snoRNA与肺癌的发生发展有密切关系。本文结合国内外snoRNA与肺癌相关的最新研究结果,在总结snoRNA的基本结构和功能的基础上,对snoRNA在肺癌发生发展中的特点以及在肺癌的诊断和治疗中潜在应用价值进行综述,以期为后续相关的研究提供参考。     

植物snoRNA

植物体含有的小分子核仁RNA(small nucleolar RNA,snoRNA)是一类典型的非编码RNA,参与rRNA的加工与修饰.该文就植物snoRNA的结构、功能、生物合成与调控研究进展作介绍.     

酿酒酵母一个新的基因簇转录多顺反子的snoRNA前体

核仁小分子RNA (snoRNA)是一类在真核生物核糖体生物合成过程中起重要作用的小分子RNA .通过计算机分析国际分子生物学数据库及实验的方法 ,在酿酒酵母 (Saccharomycescerevisiae)中发现和鉴定了一个新的snoRNA(Z8)及其特殊的基因组织 .Z8snoRNA基因位于酿酒酵母第 13号染色体上 ,是酵母snoRNA基因簇的第 1个基因 ,编码boxC/D类反义snoRNA .结构分析指出该snoRNA指导 2 5SrRNA中第 2 42 1位尿苷酸的 2′ O 核糖的甲基化 .用遗传学方法将该基因缺失后 ,其对应位点的甲基化被取消 ,但细胞的生长并未受到影响 .Z8snoRNA基因的上游 2 47位 ,有一UsnoRNA启动子保守元素 .RT PCR的结果证明 ,Z8与该基因簇中其他snoRNA(Z7和Z6)基因共同转录成一个多顺反子的snoRNA前体 ,然后再被加工成熟 ,这是一种新的snoRNA基因表达方式 .     

核仁小RNA与肺癌北大核心CSCD

核仁小RNA(small nucleolar RNA,snoRNA)是一类定位于核仁内的短链非编码RNA,在多种RNA的加工修饰过程中发挥重要作用。随着人们对基因组认识的深入,snoRNA等非编码RNA的结构及功能已成为研究的热点。近年来有研究表明,snoRNA与肺癌的发生发展有密切关系。本文结合国内外snoRNA与肺癌相关的最新研究结果,在总结snoRNA的基本结构和功能的基础上,对snoRNA在肺癌发生发展中的特点以及在肺癌的诊断和治疗中潜在应用价值进行综述,以期为后续相关的研究提供参考。     

两个保守的snoRNA基因SNORA50和SNORA71在灵长类和啮齿类的转录活性及组织表达谱

核仁小分子RNA（small nucleolar RNA,snoRNA）的主要功能是参与rRNA的修饰。最近研究表明,snoRNA可能具有广泛的生物学功能。大部分snoRNA比较保守,但也有一些snoRNA基因具有种属特异性。有意义的是,该研究发现,基因序列高度保守的snoRNA（SNORA50和SNORA71）呈现物种特异性的组织表达谱。SNORA50位于Cnot1基因内含子中,在脊椎动物中高度保守。表达谱分析发现,SNORA50在灵长类（人和恒河猴）和鸟类（鸡）的各种组织中广泛表达,但在正常发育的小鼠组织中检测不到。SNORA71位于一个非编码RNA基因snhg11的内含子中,在哺乳动物中比较保守。研究发现,SNORA71在灵长类各种组织广泛表达,而小鼠中主要在脑组织表达,与宿主基因snhg11表达谱一致。随小鼠脑发育过程的进展,SNORA71表达水平逐渐上调,提示其参与小鼠脑发育的调控。而在恒河猴从胚胎到成体的脑发育过程中,SNORA71表达没有显著的改变。这些结果表明,SNORA71对灵长类和啮齿类的神经发育可能存在不同的调控模式。基因序列保守的SNORA50和SNORA71呈现物种特异的表达模式,说明snoRNA在个体发育和系统进化中都发挥着重要的调控功能。     

非编码RNA与哺乳动物基因组印记的起源

基因组印记是由亲本来源不同而导致等位基因表达差异的一种遗传现象,主要发生在胎盘哺乳动物（真哺乳类）和显花植物中.大部分印记基因都分布在印记基因簇内,其中包含大量的非编码RNA基因.印记基因的表达受印记控制区（ICRs）的顺式调控.基因组印记产生的原因及过程是现代遗传学研究的一个热点问题,分析印记同源区从非印记物种到印记物种的过渡,为解决这一问题提供了重要启示.最近,原始哺乳动物（有袋类和单孔类）模式物种全基因组测序的完成,极大地促进了印记同源区的比较分析研究.本文对这些研究进行了回顾和分析,发现非编码RNA与哺乳动物基因组印记获得关系密切.主要依据为：（1）伴随着基因组印记的获得,印记区有大量的非编码RNA新基因出现;（2）与基因组印记相关的一些保守非编码RNA的表达发生了显著变化.此外,对15种脊椎动物中印记snoRNA基因系统分析的结果表明：印记snoRNA起源于真哺乳类与有袋类动物分化之后,并且在真哺乳类辐射进化之前发生了迅速的扩张,主要的基因家族在这一时期已经形成.这些结果进一步证明了非编码RNA与基因组印记获得的密切联系.非编码RNA可能主要通过调控印记表达和诱导染色体表观遗传修饰两种机制,参与哺乳动物基因组印记的获得.     

核仁小RNA 在肿瘤发生中的作用

核仁小RNA（small nucleolar RNA,snoRNA）是一类真核细胞核仁中的60～300个核苷酸长度的非编码RNA,主要参与rRNA和其它小RNA转录后的成熟加工过程. 它们与肿瘤的关系曾一度被人们所忽视,然而,近年来有关snoRNA新功能的研究证明,它们与肿瘤的发生、发展密切相关. snoRNA以多种方式参与肿瘤的发生：一些snoRNA（如：U50、SNORD12、SNORD12b、SNORD12c、SNORD44和h5sn2等）具有抑癌活性,而另一些snoRNA（如：SNORD33、SNORD66、SNORD76、SNORD112、SNORD113、SNORD114、SNORA42、U70C和ACA59B等）具有促癌活性. 另外,编码snoRNA基因的异常也被发现与肿瘤的发生有关. 因此,开展snoRNA与肿瘤关系的研究将有可能为肿瘤诊治提供新线索.     

植物核仁小分子RNA的研究进展

20世纪60年代末Weinberg等在哺乳动物中发现了第一个核仁小分子RNA(small nucleolar RNA,snoRNA)U3,在这一领域的研究特别是在20世纪90年代以来,陆续发现许多新的核仁小分子RNA。近几年对动物、酵母和植物方面snoRNA的研究进展,使人们大大地加深了对于rRNA加工和转录以及一系列生物调控过程和机制的认识,正如Smith和Steitz所说的那样：“核仁中sno风暴”引起生物界极大的震动。本文重点介绍植物snoRNA的研究。     

线粒体RNA转录后加工和修饰及其与人类线粒体疾病的关联

线粒体是真核细胞内参与能量生成和物质代谢的重要细胞器，拥有自身的基因组DNA。线粒体基因的表达调控对线粒体功能的维持至关重要。根据分子生物学中心法则，遗传信息是从DNA传递给RNA，再从RNA传递给蛋白质。线粒体DNA（mtDNA）编码13个信使RNA（mRNA）、2个核糖体RNA（rRNA）和22个转运RNA（tRNA）。在转录过程中，合成的各种前体RNA通常还要经历后续的改变才能转变为有活性的成熟RNA分子，这被称为“转录后的加工和修饰”。本文主要综述哺乳动物线粒体基因组编码的3种RNA转录后加工过程及修饰的方式，总结和归纳线粒体RNA修饰位点与相应的修饰酶之间的关系，并进一步探讨哺乳动物线粒体RNA转录后修饰与线粒体疾病发生发展的关联，为人类线粒体相关疾病的诊疗研究提供新的思路。     

snoRNP的生物发生

核仁小核糖核蛋白体颗粒(small nucleolar ribonucleoproteins partical,snoRNP)是一种定位于核仁的复合物,它由一系列核仁小RNA(small nucleolar RNA,snoRNA)和核心蛋白质结合而成。这些snoRNP指导核糖体RNA(rRNA)前体的加工修饰,在核糖体的生物发生中起着重要的作用。研究显示大多数snoRNP加工和组装的早期阶段发生在核浆,在Cajal小体(Cajal body,CB)中组装成熟之后,在PHAX、p50、p55、SMN和Nopp140等蛋白质的帮助下穿越各种不同的核间隔转运至核仁,并在核仁中发挥功能。本文对snoRNP的生物发生过程作一综述。     

核仁小RNA源性小RNA

最新研究结果表明,一些与RNA介导基因沉默相关的小RNA由核仁小RNA(small nucleolar RNA,snoRNA)加工产生,这种小RNA被称为核仁小RNA源性小RNA(snoRNA derived small RNA,sdRNA)。sdRNA现象分布物种广;涉及的snoRNA种类全,数量多;产生的小RNA分子大小不一、数量、种类多。表明这种小RNA在生物中存在着广泛的普遍性。sdRNA的发现拓展了snoRNA的功能,揭示了snoRNA与RNA介导的基因沉默之间的紧密关系,增强了snoRNA在RNA调控网络中的重要性,并为进一步研究RNA调控网络开启了一扇门。     

A computational screen for C/D box snoRNAs in the human genomic region associated with Prader-Willi and Angelman syndromes

Small nucleolar RNAs (snoRNAs) play a significant role in Prader-Willi Syndrome (PWS) and Angelman Syndrome (AS), which are genomic disorders resulting from deletions in the human chromosomal region 15q11–q13. To identify snoRNAs in the region, our computational study employs key motif features of C/D box snoRNAs and introduces a complementary RNA–RNA hybridization test. We identify three previously unknown methylation guide snoRNAs targeting ribosomal 18S and 28S RNAs, and two snoRNAs targeting serotonin receptor 2C mRNA. We show that the three snoRNA candidates likely possess methylation strands complementary to, and form stable complexes with, human ribosomal RNAs. Our screen also identifies 8 other snoRNA candidates that do not pass the rRNA-complementarity and/or hybridization tests. Two of these candidates have extensive sequence similarity to HBII-52, a snoRNA that regulates the alternative splicing of serotonin receptor 2C mRNA. Six out of our eleven candidate snoRNAs are also predicted by other existing methods.     

Systematic identification and characterization of porcine snoRNAs: structural,functional and developmental insights

Small nucleolar RNAs (snoRNAs) are 50‐ to 300‐nt non‐coding RNAs that are involved in critical cellular events, including rRNA/snRNA modification and splicing, ribosome genesis, telomerase formulation and cell proliferation. The identification of snoRNAs in the pig, which is a widely consumed commercial organism that also has important functions in medicine and biology, will enrich the snoRNA kingdom and provide evolutionary clues about snoRNAs. In this study, we performed a systematic identification of snoRNAs in Sus scrofa and obtained 120 candidate snoRNAs, 65 of which were predicted via sequencing from our constructed cDNA library. The others were obtained by computational screening. The primary structural features examined included the sequence length, GC content, conservation of common box motifs and nucleotide diversity. The results indicate that the primary features of H/ACA box snoRNAs are opposite to those of C/D box snoRNAs. Subsequently, based on chromosomal location and host gene determination, we assigned 91 snoRNAs to nine genome organization modes. Gene duplications and translocations are considered to contribute to the high abundant organization in evolution. Functional information about our novel snoRNAs, such as putative targets, modification sites and guide sequences, was predicted by orthologue alignment. A comparative analysis of predicted targets and possible modified loci on U6 snRNA and 5.8S and 18S rRNAs among five species revealed that targets of snoRNA are conserved among species. Furthermore, we performed a quantitative analysis of six representative snoRNA genes in two pig breeds during different developmental stages. Interestingly, all six snoRNAs from one breed expressed in a similar pattern over the tested time points; however, these same six genes had different expression patterns in the other pig breed. Specifically, expression of all six snoRNAs declined significantly from 65 to 90 days post‐coitus (dpc) and then increased slightly during adulthood in Tongcheng pigs, whereas the expression of the same six genes increased slowly from 65 dpc until adulthood in Landrace pigs. This expression pattern suggests that most housekeeping, non‐coding RNAs from a single pig breed may be similarly expressed during development. Our study adds to the knowledge about the snoRNA family by providing the first genome‐wide study of porcine snoRNAs. The comparative analysis of snoRNAs from different pig breeds gave us evolutionary insight into the function of snoRNAs.     

Mining small RNA sequencing data: a new approach to identify small nucleolar RNAs in Arabidopsis

Small nucleolar RNAs (snoRNAs) are noncoding RNAs that direct 2′-O-methylation or pseudouridylation on ribosomal RNAs or spliceosomal small nuclear RNAs. These modifications are needed to modulate the activity of ribosomes and spliceosomes. A comprehensive repertoire of snoRNAs is needed to expand the knowledge of these modifications. The sequences corresponding to snoRNAs in 18–26-nt small RNA sequencing data have been rarely explored and remain as a hidden treasure for snoRNA annotation. Here, we showed the enrichment of small RNAs at Arabidopsis snoRNA termini and developed a computational approach to identify snoRNAs on the basis of this characteristic. The approach successfully uncovered the full-length sequences of 144 known Arabidopsis snoRNA genes, including some snoRNAs with improved 5′- or 3′-end annotation. In addition, we identified 27 and 17 candidates for novel box C/D and box H/ACA snoRNAs, respectively. Northern blot analysis and sequencing data from parallel analysis of RNA ends confirmed the expression and the termini of the newly predicted snoRNAs. Our study especially expanded on the current knowledge of box H/ACA snoRNAs and snoRNA species targeting snRNAs. In this study, we demonstrated that the use of small RNA sequencing data can increase the complexity and the accuracy of snoRNA annotation.     

RNomics: an experimental approach that identifies 201 candidates for novel, small, non-messenger RNAs in mouse

In mouse brain cDNA libraries generated from small RNA molecules we have identified a total of 201 different expressed RNA sequences potentially encoding novel small non-messenger RNA species (snmRNAs). Based on sequence and structural motifs, 113 of these RNAs can be assigned to the C/D box or H/ACA box subclass of small nucleolar RNAs (snoRNAs), known as guide RNAs for rRNA. While 30 RNAs represent mouse homologues of previously identified human C/D or H/ACA snoRNAs, 83 correspond to entirely novel snoRNAS: Among these, for the first time, we identified four C/D box snoRNAs and four H/ACA box snoRNAs predicted to direct modifications within U2, U4 or U6 small nuclear RNAs (snRNAs). Furthermore, 25 snoRNAs from either class lacked antisense elements for rRNAs or snRNAS: Therefore, additional snoRNA targets have to be considered. Surprisingly, six C/D box snoRNAs and one H/ACA box snoRNA were expressed exclusively in brain. Of the 88 RNAs not belonging to either snoRNA subclass, at least 26 are probably derived from truncated heterogeneous nuclear RNAs (hnRNAs) or mRNAS: Short interspersed repetitive elements (SINEs) are located on five RNA sequences and may represent rare examples of transcribed SINES: The remaining RNA species could not as yet be assigned either to any snmRNA class or to a part of a larger hnRNA/mRNA. It is likely that at least some of the latter will represent novel, unclassified snmRNAS: