کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5675404 | 1594323 | 2017 | 41 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Structural insights into RNA synthesis by the influenza virus transcription-replication machine
دانلود مقاله + سفارش ترجمه
دانلود مقاله ISI انگلیسی
رایگان برای ایرانیان
کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
ایمنی شناسی و میکروب شناسی
ویروس شناسی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Structural insights into RNA synthesis by the influenza virus transcription-replication machine Structural insights into RNA synthesis by the influenza virus transcription-replication machine](/preview/png/5675404.png)
چکیده انگلیسی
Influenza virus is a segmented, negative strand RNA virus with each genome segment being packaged in a distinct ribonucleoprotein particle (RNP). The RNP consists of the heterotrimeric viral RNA-dependent RNA polymerase bound to the conserved 5â² and 3â² ends of the genome segment (the viral promoter) with the rest of the viral RNA (vRNA) being covered by multiple copies of nucleoprotein. This review focusses on the new insights that recent crystal structures have given into the detailed molecular mechanisms by which the polymerase performs both transcription and replication of the vRNA genome. Promoter binding, in particular that of 5â² end, is essential to allosterically activate all polymerase functions. Transcription is initiated by the hijacking of nascent, capped host transcripts by the process of 'cap-snatching', for which the viral polymerase makes an essential interaction with the C-terminal domain (CTD) of cellular RNA polymerase II. The structures allow a coherent mechanistic model of the subsequent cap-snatching, cap-dependent priming, elongation and self-polyadenylation steps of viral mRNA synthesis. During replication, the vRNA is copied without modification into complementary RNA (cRNA) which is packaged into cRNPs. A priming loop located in the polymerase active site is required for the unprimed synthesis of cRNA from vRNA, but is not required for cRNA to vRNA replication due to differences in the mode of initiation of RNA synthesis. Overall a picture emerges of influenza polymerase being a highly complex, flexible and dynamic machine. The challenge remains to understand in more detail how it functions within the RNP and how interacting host factors modulate its activity in the cellular context. Finally, these detailed insights have opened up new opportunities for structure-based antiviral drug design targeting multiple aspects of polymerase function.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Virus Research - Volume 234, 15 April 2017, Pages 103-117
Journal: Virus Research - Volume 234, 15 April 2017, Pages 103-117
نویسندگان
Alexander Pflug, Maria Lukarska, Patricia Resa-Infante, Stefan Reich, Stephen Cusack,