Baidu
map

Cell Research:环装RNA编码蛋白的重要机制

2017-03-16 上海生命科学研究院 上海生命科学研究院

  3月10,中国科学院-马普学会计算生物学伙伴研究所研究员王泽峰在《细胞研究》(Cell Research)上在线发表了题为Extensive translation of circular RNAs driven by N6-methyladenosine 的研究论文,该研究发现了大量的环形RNA可作为信使RNA来编码蛋白,这些环形信使RNA通过一种常见的RNA甲基化修饰m

 

3月10,中国科学院-马普学会计算生物学伙伴研究所研究员王泽峰在《细胞研究》(Cell Research)上在线发表了题为Extensive translation of circular RNAs driven by N6-methyladenosine 的研究论文,该研究发现了大量的环形RNA可作为信使RNA来编码蛋白,这些环形信使RNA通过一种常见的RNA甲基化修饰m6A,来驱动非帽依赖性的翻译机制来合成蛋白质。该研究进一步拓展了环装RNA的功能,对蛋白质来源的多样性有新的认识,具有十分重要的理论意义。

环状RNA在某些病毒中普遍存在,然而近年才在真核生物中发现大量这种非主流RNA。人类的环状RNA主要是由外显子的反向剪接产生的,但关于其生物功能尚无定论。先前研究显示,环状RNA是一种非编码RNA,可以如同海绵一样吸附miRNA或RNA结合蛋白,从而起到调控基因表达的作用。

人的细胞中所有的已知mRNA都含有5'端帽结构,这一帽结构是大部分mRNA翻译所必需的。然而在一些特殊情况如细胞应激条件下,有些mRNA可以不依赖于帽结构而靠一个叫IRSE的顺式调控原件从mRNA的中间启动翻译。这种IRES驱动的蛋白翻译在RNA病毒中很常见,但只在一小部分的真核细胞mRNA中发现。在王泽峰组的前期工作中,他们发现插有IRES的编码GFP的环状RNA可以在细胞中被翻译。而新的工作中,他们发现环状RNA中富含m6A甲基化修饰,而且这些碱基修饰可以像IRES一样驱动环状RNA翻译。王泽峰认为,"这两个发现放在一起,就可推断出有大量的环状RNA被翻译成蛋白质这一令人惊讶的结论,说明人的细胞中存在有大量的环状RNA编码的未知蛋白。"这是一个很令人兴奋的结论,说明人类蛋白质的多样性远比从前想的大。

该文作者们进一步研究了环形RNA的翻译机制,发现了m6A识别蛋白YTHDF3能够结合到环状RNA的修饰位点并募集eIF4G2和其他翻译起始因子来驱动环状RNA的翻译。同时,他们通过多核糖体分析和RNA测序发现大量的环状RNA与多核糖体结合在一起。在此基础上,利用质谱分析的方法鉴定了一些由环状RNA反向剪接接口编码的新肽段。

尽管不排除很多环状RNA仍可能是非编码RNA,但新结果证明其中一大部分可以像信使RNA一样翻译成蛋白。"这一发现模糊了编码和非编码RNA的界定。"王泽峰认为,"信使RNA不见得一定需要是线性的,环状RNA显然是一类新的信使RNA。"

新文章尚未解答的重要问题是这些环状RNA编码的蛋白功能是什么,但他们提出了一些有趣的可能性。正常情况下,真核细胞中蛋白质合成的主要方式是通过5'端帽依赖性翻译,但在应激环境下或一些癌症中,5'端帽依赖性翻译会被抑制而非帽依赖性翻译将会取代。因为环状RNA没有5'端帽结构,所以所有的环状RNA翻译都是通过非5'端帽依赖性翻译进行的。因而环状RNA可能通过产生刺激诱导蛋白在细胞应激反应中发挥重要作用。根据类似推理,环状RNA编码的蛋白可能在癌症发展过程中发挥重要作用。

此项研究和之前的研究都表明m6A可以像IRES一样启动翻译,而在信使RNA中存在大量的m6A修饰。因此王泽峰相信:"类似于一个基因可以通过可变剪接产生多个信使RNA异构体一样,一个信使RNA可能通过非帽依赖性翻译产生多种蛋白质。"

参与此项工作的合作者包括来自浙江大学、中科院上海生命科学研究院生物化学与细胞生物学研究所、华东理工大学和大连医科大学的科学家。

原始出处:

Yang Y, Fan X, Mao M,et al. Extensive translation of circular RNAs driven by N6-methyladenosine.Cell Res. 2017 Mar 10.

版权声明:
本网站所有内容来源注明为“梅斯医学”或“MedSci原创”的文字、图片和音视频资料,版权均属于梅斯医学所有。非经授权,任何媒体、网站或个人不得转载,授权转载时须注明来源为“梅斯医学”。其它来源的文章系转载文章,或“梅斯号”自媒体发布的文章,仅系出于传递更多信息之目的,本站仅负责审核内容合规,其内容不代表本站立场,本站不负责内容的准确性和版权。如果存在侵权、或不希望被转载的媒体或个人可与我们联系,我们将立即进行删除处理。
在此留言
评论区 (5)
#插入话题
  1. [GetPortalCommentsPageByObjectIdResponse(id=1960062, encodeId=a7101960062cd, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=102, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4454, encryptionId=dbe6445416, topicName=CEL)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c3ff68, createdName=维他命, createdTime=Sun Dec 03 06:33:00 CST 2017, time=2017-12-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1869803, encodeId=54211869803b3, content=<a href='/topic/show?id=fd764459a8' target=_blank style='color:#2F92EE;'>#Cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=64, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4459, encryptionId=fd764459a8, topicName=Cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=524d95, createdName=zhaozhouchifen, createdTime=Thu Apr 13 04:33:00 CST 2017, time=2017-04-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1557757, encodeId=b01b155e757b0, content=<a href='/topic/show?id=d2601533982' target=_blank style='color:#2F92EE;'>#Research#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=107, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15339, encryptionId=d2601533982, topicName=Research)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=96ab14929432, createdName=yangshch, createdTime=Sat Mar 18 06:33:00 CST 2017, time=2017-03-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1584654, encodeId=033215846547b, content=<a href='/topic/show?id=83f5e9250e9' target=_blank style='color:#2F92EE;'>#编码#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=105, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=79250, encryptionId=83f5e9250e9, topicName=编码)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=b10a17056098, createdName=12498f6em12暂无昵称, createdTime=Sat Mar 18 06:33:00 CST 2017, time=2017-03-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=180405, encodeId=6a041804055e, content=lncRNA是热点,但不见得是靶点,尤其是药物靶点, beContent=null, objectType=article, channel=null, level=null, likeNumber=143, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20170206/IMG589879E392F941842.jpg, createdBy=f4d469996, createdName=wangyunyb, createdTime=Thu Mar 16 20:08:34 CST 2017, time=2017-03-16, status=1, ipAttribution=)]
    2017-12-03 维他命
  2. [GetPortalCommentsPageByObjectIdResponse(id=1960062, encodeId=a7101960062cd, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=102, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4454, encryptionId=dbe6445416, topicName=CEL)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c3ff68, createdName=维他命, createdTime=Sun Dec 03 06:33:00 CST 2017, time=2017-12-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1869803, encodeId=54211869803b3, content=<a href='/topic/show?id=fd764459a8' target=_blank style='color:#2F92EE;'>#Cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=64, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4459, encryptionId=fd764459a8, topicName=Cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=524d95, createdName=zhaozhouchifen, createdTime=Thu Apr 13 04:33:00 CST 2017, time=2017-04-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1557757, encodeId=b01b155e757b0, content=<a href='/topic/show?id=d2601533982' target=_blank style='color:#2F92EE;'>#Research#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=107, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15339, encryptionId=d2601533982, topicName=Research)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=96ab14929432, createdName=yangshch, createdTime=Sat Mar 18 06:33:00 CST 2017, time=2017-03-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1584654, encodeId=033215846547b, content=<a href='/topic/show?id=83f5e9250e9' target=_blank style='color:#2F92EE;'>#编码#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=105, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=79250, encryptionId=83f5e9250e9, topicName=编码)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=b10a17056098, createdName=12498f6em12暂无昵称, createdTime=Sat Mar 18 06:33:00 CST 2017, time=2017-03-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=180405, encodeId=6a041804055e, content=lncRNA是热点,但不见得是靶点,尤其是药物靶点, beContent=null, objectType=article, channel=null, level=null, likeNumber=143, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20170206/IMG589879E392F941842.jpg, createdBy=f4d469996, createdName=wangyunyb, createdTime=Thu Mar 16 20:08:34 CST 2017, time=2017-03-16, status=1, ipAttribution=)]
  3. [GetPortalCommentsPageByObjectIdResponse(id=1960062, encodeId=a7101960062cd, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=102, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4454, encryptionId=dbe6445416, topicName=CEL)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c3ff68, createdName=维他命, createdTime=Sun Dec 03 06:33:00 CST 2017, time=2017-12-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1869803, encodeId=54211869803b3, content=<a href='/topic/show?id=fd764459a8' target=_blank style='color:#2F92EE;'>#Cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=64, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4459, encryptionId=fd764459a8, topicName=Cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=524d95, createdName=zhaozhouchifen, createdTime=Thu Apr 13 04:33:00 CST 2017, time=2017-04-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1557757, encodeId=b01b155e757b0, content=<a href='/topic/show?id=d2601533982' target=_blank style='color:#2F92EE;'>#Research#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=107, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15339, encryptionId=d2601533982, topicName=Research)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=96ab14929432, createdName=yangshch, createdTime=Sat Mar 18 06:33:00 CST 2017, time=2017-03-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1584654, encodeId=033215846547b, content=<a href='/topic/show?id=83f5e9250e9' target=_blank style='color:#2F92EE;'>#编码#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=105, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=79250, encryptionId=83f5e9250e9, topicName=编码)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=b10a17056098, createdName=12498f6em12暂无昵称, createdTime=Sat Mar 18 06:33:00 CST 2017, time=2017-03-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=180405, encodeId=6a041804055e, content=lncRNA是热点,但不见得是靶点,尤其是药物靶点, beContent=null, objectType=article, channel=null, level=null, likeNumber=143, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20170206/IMG589879E392F941842.jpg, createdBy=f4d469996, createdName=wangyunyb, createdTime=Thu Mar 16 20:08:34 CST 2017, time=2017-03-16, status=1, ipAttribution=)]
  4. [GetPortalCommentsPageByObjectIdResponse(id=1960062, encodeId=a7101960062cd, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=102, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4454, encryptionId=dbe6445416, topicName=CEL)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c3ff68, createdName=维他命, createdTime=Sun Dec 03 06:33:00 CST 2017, time=2017-12-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1869803, encodeId=54211869803b3, content=<a href='/topic/show?id=fd764459a8' target=_blank style='color:#2F92EE;'>#Cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=64, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4459, encryptionId=fd764459a8, topicName=Cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=524d95, createdName=zhaozhouchifen, createdTime=Thu Apr 13 04:33:00 CST 2017, time=2017-04-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1557757, encodeId=b01b155e757b0, content=<a href='/topic/show?id=d2601533982' target=_blank style='color:#2F92EE;'>#Research#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=107, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15339, encryptionId=d2601533982, topicName=Research)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=96ab14929432, createdName=yangshch, createdTime=Sat Mar 18 06:33:00 CST 2017, time=2017-03-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1584654, encodeId=033215846547b, content=<a href='/topic/show?id=83f5e9250e9' target=_blank style='color:#2F92EE;'>#编码#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=105, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=79250, encryptionId=83f5e9250e9, topicName=编码)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=b10a17056098, createdName=12498f6em12暂无昵称, createdTime=Sat Mar 18 06:33:00 CST 2017, time=2017-03-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=180405, encodeId=6a041804055e, content=lncRNA是热点,但不见得是靶点,尤其是药物靶点, beContent=null, objectType=article, channel=null, level=null, likeNumber=143, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20170206/IMG589879E392F941842.jpg, createdBy=f4d469996, createdName=wangyunyb, createdTime=Thu Mar 16 20:08:34 CST 2017, time=2017-03-16, status=1, ipAttribution=)]
  5. [GetPortalCommentsPageByObjectIdResponse(id=1960062, encodeId=a7101960062cd, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=102, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4454, encryptionId=dbe6445416, topicName=CEL)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c3ff68, createdName=维他命, createdTime=Sun Dec 03 06:33:00 CST 2017, time=2017-12-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1869803, encodeId=54211869803b3, content=<a href='/topic/show?id=fd764459a8' target=_blank style='color:#2F92EE;'>#Cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=64, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4459, encryptionId=fd764459a8, topicName=Cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=524d95, createdName=zhaozhouchifen, createdTime=Thu Apr 13 04:33:00 CST 2017, time=2017-04-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1557757, encodeId=b01b155e757b0, content=<a href='/topic/show?id=d2601533982' target=_blank style='color:#2F92EE;'>#Research#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=107, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15339, encryptionId=d2601533982, topicName=Research)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=96ab14929432, createdName=yangshch, createdTime=Sat Mar 18 06:33:00 CST 2017, time=2017-03-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1584654, encodeId=033215846547b, content=<a href='/topic/show?id=83f5e9250e9' target=_blank style='color:#2F92EE;'>#编码#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=105, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=79250, encryptionId=83f5e9250e9, topicName=编码)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=b10a17056098, createdName=12498f6em12暂无昵称, createdTime=Sat Mar 18 06:33:00 CST 2017, time=2017-03-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=180405, encodeId=6a041804055e, content=lncRNA是热点,但不见得是靶点,尤其是药物靶点, beContent=null, objectType=article, channel=null, level=null, likeNumber=143, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20170206/IMG589879E392F941842.jpg, createdBy=f4d469996, createdName=wangyunyb, createdTime=Thu Mar 16 20:08:34 CST 2017, time=2017-03-16, status=1, ipAttribution=)]
    2017-03-16 wangyunyb

    lncRNA是热点,但不见得是靶点,尤其是药物靶点

    0

相关资讯

Cell:“垃圾”RNA不垃圾,帮助细胞应对压力

非编码RNA通常因不能编码蛋白质的RNA而被称为“垃圾RNA” ,包括小RNA以及长链RNA。近期,来自于哈佛大学医学院附属麻省总医院(MGH)的研究团队却发现,“垃圾”RNA并不垃圾,它通过与一种负责基因沉默的酶互作,确保应激基因的表达,促使细胞对抗胁迫。研究人员发现的“垃圾”RNA是B2 RNA,由B2 SINE 反转录转座子转录而来的RNA。而与它发生互作的关键酶类是EZH2,起始复合体2(

今天的RNA-based疗法,犹如1997年的单抗

近年来,RNA-based疗法在遗传病、罕见病领域的成效越来越显著。在过去的7年里,我们见证了3例反义寡核苷酸的获批,包括几个月前获批的Exondys 51和Spinraza。首个小干扰RNA(siRNA)疗法有望在下一年问世。

Nature:母体取血,揭示胚胎奥秘

从母体采集一点点血液,利用最先进的分子技术,就可以揭秘胎儿发育的秘密。

Nature Methods:便携、低成本的单细胞RNA测序新手段

每个细胞的基因表达谱随其功能而异。从血液或组织样本中的许多单个细胞中提取RNA可以根据基因表达模式区分细胞。这使科学家有机会确定细胞功能,包括它们在疾病中的作用或对治疗的反应。MIT的研究人员已经开发出一种便携式技术,可以快速制备多种细胞的RNA同时进行测序,他们相信这种方法将会更广泛地被应用。新的技术被称为Seq-Well,可以让科学家在组织样本中更容易识别不同类型的细胞,帮助他们研究免疫细胞如

Cancer Res:揭示肺癌成功转移到大脑中的分子机制

每年因肺癌死亡的人要远远多于因乳腺癌、结肠癌以及前列腺癌死亡的人数,肺癌的一种特殊致死性形式是肺腺癌(LUAD),其影响着吸烟和非吸烟人群的健康,在很多被诊断为肺腺癌的患者中,其机体中的肿瘤细胞已经扩散到了大脑中,这样就会明显降低患者的生活质量以及生存率。 日前,一项刊登在国际杂志

张锋发现靶向RNA“新魔剪”,CRISPR家族再次壮大!

近日,发表在Molecular Cell杂志上题为“Cas13b Is a Type VI-B CRISPR-Associated RNA-Guided RNase Differentially Regulated by Accessory Proteins Csx27 and Csx28”的研究中,张锋带领的研究小组发现了两个新型的RNA靶向CRISPR系统。这类新系统利用了一种新的Cas酶——

Baidu
map
Baidu
map
Baidu
map