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Basic Characteristics of Mutations
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Mutation Site
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R38A |
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Mutation Site Sentence
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As shown in Figure 3C, the PB2-R38A, PB1-L675A/N676A and PB1-L675A/N676A/PB2-R38A mutant FluPols produced even more transcripts than the WT FluPols, indicating that the reduction in transcription products observed in the in vivo RNP reconstitution and primer extension assay is not due to defects in the initiation and early elongation stages of transcription. |
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Mutation Level
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Amino acid level |
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Mutation Type
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Nonsynonymous substitution |
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Gene/Protein/Region
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PB2 |
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Standardized Encoding Gene
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PB2
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Genotype/Subtype
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H5N1 |
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Viral Reference
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-
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Functional Impact and Mechanisms
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Disease
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Cell line
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Immune
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- |
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Target Gene
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-
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Clinical and Epidemiological Correlations
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Clinical Information
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- |
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Treatment
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- |
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Location
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China |
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Literature Information
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PMID
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39676676
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Title
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Mutagenesis studies suggest a mechanism for influenza polymerase stalling during polyadenylation
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Author
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Li M,Wu Y,Li H,Song W,Chen Z,Peng Y,Yang B,Xu C,Zhang J,Xing L,Weng Z,Liu Y,Liang H
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Journal
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Nucleic acids research
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Journal Info
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2025 Jan 24;53(3):gkae1225
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Abstract
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Influenza polymerase (FluPol) carries out both viral transcription and replication using the same viral genome segment as a template to yield distinct end products. However, it remains largely unclear how FluPol synthesizes transcripts containing poly (A) tails during transcription termination, while producing fully complementary products during replication termination. In this study, through structural analysis combined with cell-based and biochemical assays, we identified that the PB1 Leu675/Asn676 and PB2 Arg38 residues of FluPol are critical for transcription termination and polyadenylation. During transcription termination, these three residues adopt the PB1 Leu675/Asn676down and PB2 Arg38out conformations, with their side chains positioned against the G12 and G14 residues of the RNA template at the 5' end. These steric hindrances block template translocation and facilitate FluPol 'stuttering' at U17, which is required for viral messenger RNA polyadenylation. Importantly, both structural analysis and mutational studies suggest that this specific conformation of these residues is unique to the transcription termination state. Overall, our findings provide novel insights into the mechanisms by which FluPol generates distinct 3' end products during transcription and replication termination.
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Sequence Data
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-
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