摘要:Case Western Reserve医学院识别出了一种细胞机制,该机制对于维持细胞正常功能来讲是很关键的。该大学RNA分子生物学中心Eckhard Jankowsky博士领导这项研究,并对TRAMP的功能进行了鉴定,该蛋白复合物参与了细胞中核糖核酸(RNA)的装配和加工过程。 他们确定了Mtr4p蛋白的一个关键性功能,即引发选择性RNA的降解,这是维护正常细胞功能的一个必要步骤。这项研究结果发表于6月9日的《细胞》,第一作者是Jankowsky博士。
TRAMP蛋白复合物能够识别RNA的降解,它会通过添加一段腺苷来标记RNA,用来标记的腺苷的数量是有限制的,携带过多腺苷的RNAs不能在降解中被识别出来。
文章中,研究人员详细说明了解旋酶是如何控制追加的腺苷数量:Mtr4p会根据腺苷(4~5)的数量,用聚合酶追加,然后对聚合酶的活性做相应的调整。
Jankowsky说:“我们的工作阐明了细胞机制中非常重要的一步,即细胞核中对RNA降解的标记,适当的标记对于细胞功能是至关重要的。”
生物探索推荐英文原文:
Key Function of Enzyme Involved in RNA Processing Described
Researchers at the Case Western Reserve University School of Medicine have identified a cellular mechanism that is critical in maintaining normal cell function.
In their work, the researchers led by Eckhard Jankowsky, PhD, researcher and associate professor in the Center for RNA Molecular Biology at the Case Western Reserve University School of Medicine, examined the function of TRAMP, a protein complex involved in the processing of RNA or ribonucleic acid within the cell. They identified a key function for the protein Mtr4p in a process that initiates the degradation of select RNAs, a necessary step in preserving normal cell function.
The research findings appear in the June 9 issue of the journal Cell. Dr. Jankowsky is the senior author.
Cellular function requires a multitude of different types of RNA that need to be correctly processed and assembled into functional complexes.
"RNA that is improperly assembled, defective, or no longer needed, looks very similar to RNA that is being used," Dr. Jankowsky said. "So, improperly assembled, defective, or no longer needed RNA can readily interfere with ongoing processes. To avoid this, there are several very efficient RNA degradation pathways, and one of these is initiated by TRAMP."
The TRAMP complex identifies the RNAs slated for degradation and tags them with a stretch of adenosines, one of the four nucleotides of which RNA is made. The number of adenosines in the tag has to be limited, because RNAs with too many adenosines are no longer recognized as targets for degradation.
Dr. Jankowsky and the team of researchers that included Huijue Jia, a graduate student at the School of Medicine, and Jim Anderson, associate professor of Marquette University, a key collaborator and instrumental figure in the discovery of the TRAMP complex, studied the molecular mechanism how the TRAMP complex marks RNAs. TRAMP is composed of the enzyme poly(A) polymerase Trf4p, the Zn-knuckle protein Air2p, and Mtr4p, a RNA helicase. Helicases unwind helices, but in TRAMP, the researchers found, the helicase Mtr4p controls the number of adenosines added.
In their paper, the researchers detail how the helicase controls the number of the adenosines that are appended. Mtr4p counts the number of adenosines (between four and five) that have been appended by the polymerase, and then adjusts the polymerase activity accordingly.
"Our work explains an important step in the mechanism by which cells mark RNAs for degradation in the nucleus," Dr. Jankowsky said. "Appropriate tagging is critical for cell function."
The research, which took place in Dr. Jankowsky's lab in the Center for RNA Molecular Biology at Case Western Reserve University School of Medicine, establishes a basis for future research to examine the steps between tagging RNA and the actual RNA degradation by other enzymes that are involved in this process.