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10.1021/acs.accounts.6b00151 http://scihub22266oqcxt.onion/10.1021/acs.accounts.6b00151 C5305810!5305810 !27269119     free     free     free Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 245.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 245.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 245.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 245.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 245.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 245.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 245.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\27269119 .jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117       Acc+Chem+Res 2016 ; 49 (6 ): 1242-9 Nephropedia Template TP {{tp|p=27269119 |t=2016. Discriminating Self and Non-Self by RNA: Roles for RNA Structure, Misfolding, and Modification in Regulating the Innate Immune Sensor PKR |pdf=|usr=}}{{27269119 }} gab.com Text Discriminating Self and Non-Self by RNA: Roles for RNA Structure, Misfolding, and Modification in Regulating the Innate Immune Sensor PKR JO: Acc Chem Res http://www.kidney.de/pget.php?&tw=1&pmid=27269119 #FOAvip Pathogens are recognized by the innate immune system in part via their unique and complex RNA signatures. A key sensor in human innate immunity is the RNA-activated protein kinase, protein kinase R (PKR), which has two double-stranded RNA (dsRNA) binding motifs (dsRBMs) at its N-terminus. Early studies described PKR as being activated potently by long stretches of perfect dsRNA, a signature typical of viruses. More recently, we and others have found that PKR is also activated by RNAs having structural defects such as bulges and internal loops. This Account describes advances in our understanding of the ability of PKR to detect diverse foreign RNAs and how that recognition plays significant roles in discriminating self from non-self. The experiments discussed employ a wide range of techniques including activation assays, native polyacrylamide gel electrophoresis (PAGE), protein footprinting, and small-angle X-ray scattering (SAXS). We discuss how misfolding and dimerization of RNA lead to activation of PKR. We also present recent findings on the activation of PKR by varied bacterial functional RNAs including ribozymes and riboswitches, which are among the few structured RNAs known to interact with PKR in a site-specific manner. Molecular models for how these structured RNAs activate PKR are provided. Studies by SAXS revealed that PKR straightens bent RNAs. Most external and internal RNA cellular modifications introduced in vitro and found naturally, such as the m7G cap and m6A group, abrogate activation of PKR, but other modifications, such as 5'-ppp and 2'-fluoro groups, are immunostimulatory and potential anticancer agents. Genome-wide studies of RNA folding in vitro and in vivo have provided fresh insights into general differences in RNA structure among bacteria, viruses, and human. These studies suggest that in vivo, cellular human RNAs are less folded than once thought, unwound by helicases, destabilized by m6A modifications, and often bound up with proteins, all conditions known to abrogate activation of PKR. It thus appears that non-self RNAs are detected as unmodified, naked RNAs with appreciable secondary and tertiary structure. Observation that PKR is activated by structured but otherwise diverse RNAs is consistent both with the broad-spectrum nature of innate immunity and the nonspecific recognition of RNA by the dsRBM family. These findings provide a possible explanation for the apparent absence of protein-free structured human RNAs, such as ribozymes and riboswitches. Twit Text FOAVip Discriminating Self and Non-Self by RNA: Roles for RNA Structure, Misfolding, and Modification in Regulating the Innate Immune Sensor PKR ????Acc Chem Res http://www.kidney.de/pget.php?&tw=1&pmid=27269119 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=27269119 #FOAvip English Wikipedia <ref>{{Cite pmid|27269119 }}</ref> Discriminating Self and Non-Self by RNA: Roles for RNA Structure, Misfolding, and Modification in Regulating the Innate Immune Sensor PKR #MMPMID27269119 Hull CM ; Bevilacqua PC Acc Chem Res 2016[Jun]; 49 (6 ): 1242-9 PMID27269119 show ga Pathogens are recognized by the innate immune system in part via their unique and complex RNA signatures. A key sensor in human innate immunity is the RNA-activated protein kinase, protein kinase R (PKR), which has two double-stranded RNA (dsRNA) binding motifs (dsRBMs) at its N-terminus. Early studies described PKR as being activated potently by long stretches of perfect dsRNA, a signature typical of viruses. More recently, we and others have found that PKR is also activated by RNAs having structural defects such as bulges and internal loops. This Account describes advances in our understanding of the ability of PKR to detect diverse foreign RNAs and how that recognition plays significant roles in discriminating self from non-self. The experiments discussed employ a wide range of techniques including activation assays, native polyacrylamide gel electrophoresis (PAGE), protein footprinting, and small-angle X-ray scattering (SAXS). We discuss how misfolding and dimerization of RNA lead to activation of PKR. We also present recent findings on the activation of PKR by varied bacterial functional RNAs including ribozymes and riboswitches, which are among the few structured RNAs known to interact with PKR in a site-specific manner. Molecular models for how these structured RNAs activate PKR are provided. Studies by SAXS revealed that PKR straightens bent RNAs. Most external and internal RNA cellular modifications introduced in vitro and found naturally, such as the m7G cap and m6A group, abrogate activation of PKR, but other modifications, such as 5'-ppp and 2'-fluoro groups, are immunostimulatory and potential anticancer agents. Genome-wide studies of RNA folding in vitro and in vivo have provided fresh insights into general differences in RNA structure among bacteria, viruses, and human. These studies suggest that in vivo, cellular human RNAs are less folded than once thought, unwound by helicases, destabilized by m6A modifications, and often bound up with proteins, all conditions known to abrogate activation of PKR. It thus appears that non-self RNAs are detected as unmodified, naked RNAs with appreciable secondary and tertiary structure. Observation that PKR is activated by structured but otherwise diverse RNAs is consistent both with the broad-spectrum nature of innate immunity and the nonspecific recognition of RNA by the dsRBM family. These findings provide a possible explanation for the apparent absence of protein-free structured human RNAs, such as ribozymes and riboswitches. |*Immunity, Innate [MESH] |*Nucleic Acid Conformation [MESH] |Dimerization [MESH] |Enzyme Activation [MESH] |RNA/*chemistry [MESH]Discriminating Self and Non-Self by RNA: Roles for RNA Structure, Misf(epmc).pdf DeepDyve Pubget Overpricing