Regulation of the interferon-inducible eIF-2α protein kinase by small RNAs

Movements of HIV-1 genomic RNA-APOBEC3F complexes and PKR reveal cytoplasmic and nuclear PKR defenses and HIV-1 evasion strategies

“…Our conclusion that SG formation is PKR dependent and requires a suprathreshold concentration of cytoplasmic gRNA is compatible with evidence that cells contain endogenous PKR inhibitors including proteins with dsRBDs and inhibitory RNAs (Bannwarth and Gatignol, 2005; Brand et al, 1997; Cai et al, 2000; Clemens et al, 1994; Clerzius et al, 2009; Clerzius et al, 2011; Clerzius et al, 2013; Daher et al, 2009; Endo-Munoz et al, 2005; Ong et al, 2005; Samuel, 1992; Sanghvi and Steel, 2011; Singh et al, 2011). Those studies principally analyzed levels of PKR-P and other proteins in post-nuclear cytoplasmic extracts from whole cell cultures.…”

“…Many viruses have evolved mechanisms to suppress SGs by limiting synthesis and nuclear export of viral mRNAs and/or by inactivating factors needed for SG assembly or stability (Abrahamyan et al, 2010; Bannwarth and Gatignol, 2005; Brand et al, 1997; Cai et al, 2000; Clemens et al, 1994; Clerzius et al, 2011; Courtney et al, 2012; Emara and Brinton, 2007; Fros et al, 2012; Gordon et al, 2013; Kedersha and Anderson, 2007; McInerney et al, 2005; Montero et al, 2008; Nallagatla et al, 2011; Sanghvi and Steel, 2011; Simpson-Holley et al, 2011; White and Lloyd, 2012). Consequently, it has been proposed that SGs function in part as antiviral defense granules to inhibit translation, block mitosis, and prime cells for apoptosis in response to cytoplasmic surges of viral factors, and that extant viruses have necessarily evolved mechanisms to evade this innate intracellular defense.…”

Movements of HIV-1 genomic RNA-APOBEC3F complexes and PKR reveal cytoplasmic and nuclear PKR defenses and HIV-1 evasion strategies

“…Our conclusion that SG formation is PKR dependent and requires a suprathreshold concentration of cytoplasmic gRNA is compatible with evidence that cells contain endogenous PKR inhibitors including proteins with dsRBDs and inhibitory RNAs (Bannwarth and Gatignol, 2005; Brand et al, 1997; Cai et al, 2000; Clemens et al, 1994; Clerzius et al, 2009; Clerzius et al, 2011; Clerzius et al, 2013; Daher et al, 2009; Endo-Munoz et al, 2005; Ong et al, 2005; Samuel, 1992; Sanghvi and Steel, 2011; Singh et al, 2011). Those studies principally analyzed levels of PKR-P and other proteins in post-nuclear cytoplasmic extracts from whole cell cultures.…”

“…Many viruses have evolved mechanisms to suppress SGs by limiting synthesis and nuclear export of viral mRNAs and/or by inactivating factors needed for SG assembly or stability (Abrahamyan et al, 2010; Bannwarth and Gatignol, 2005; Brand et al, 1997; Cai et al, 2000; Clemens et al, 1994; Clerzius et al, 2011; Courtney et al, 2012; Emara and Brinton, 2007; Fros et al, 2012; Gordon et al, 2013; Kedersha and Anderson, 2007; McInerney et al, 2005; Montero et al, 2008; Nallagatla et al, 2011; Sanghvi and Steel, 2011; Simpson-Holley et al, 2011; White and Lloyd, 2012). Consequently, it has been proposed that SGs function in part as antiviral defense granules to inhibit translation, block mitosis, and prime cells for apoptosis in response to cytoplasmic surges of viral factors, and that extant viruses have necessarily evolved mechanisms to evade this innate intracellular defense.…”

Ribosomal protein L22 inhibits regulation of cellular activities by the Epstein‐Barr virus small RNA EBER‐1

“…5A (lower panel, lanes 7 and 8). The latter figure also illustrates that L22 alone had no effect either on basal PKR activity (upper panel, lane 1 vs. lanes 3-5) or on the activation of the protein kinase by poly(I).poly(C) (lane 2 vs. lanes [6][7][8]. Figure 5B provides confirmation that the protein which is phosphorylated when recombinant L22 is added to assays containing active PKR is indeed the ribosomal protein itself.…”

A dynamically tuned double‐stranded RNA binding mechanism for the activation of antiviral kinase PKR

“…Indeed, PKR is known to recognize a variety of viral dsRNAs, including structured RNAs that contain only short segments of uninterrupted Watson–Crick base pairing, such as HIV‐Tar, adenovirus VAI RNA, EBV RNAs, EBER‐1 and EBER‐2, etc. (Clemens et al ., 1994). In fact, a more recent systematic study has documented that PKR can bind dsRNAs with secondary structure defects such as a GA:AG mismatch and non‐contiguous helix (Bevilacqua et al ., 1998).…”

Movements of HIV-1 genomic RNA-APOBEC3F complexes and PKR reveal cytoplasmic and nuclear PKR defenses and HIV-1 evasion strategies

“…Our conclusion that SG formation is PKR dependent and requires a suprathreshold concentration of cytoplasmic gRNA is compatible with evidence that cells contain endogenous PKR inhibitors including proteins with dsRBDs and inhibitory RNAs (Bannwarth and Gatignol, 2005; Brand et al, 1997; Cai et al, 2000; Clemens et al, 1994; Clerzius et al, 2009; Clerzius et al, 2011; Clerzius et al, 2013; Daher et al, 2009; Endo-Munoz et al, 2005; Ong et al, 2005; Samuel, 1992; Sanghvi and Steel, 2011; Singh et al, 2011). Those studies principally analyzed levels of PKR-P and other proteins in post-nuclear cytoplasmic extracts from whole cell cultures.…”

“…Many viruses have evolved mechanisms to suppress SGs by limiting synthesis and nuclear export of viral mRNAs and/or by inactivating factors needed for SG assembly or stability (Abrahamyan et al, 2010; Bannwarth and Gatignol, 2005; Brand et al, 1997; Cai et al, 2000; Clemens et al, 1994; Clerzius et al, 2011; Courtney et al, 2012; Emara and Brinton, 2007; Fros et al, 2012; Gordon et al, 2013; Kedersha and Anderson, 2007; McInerney et al, 2005; Montero et al, 2008; Nallagatla et al, 2011; Sanghvi and Steel, 2011; Simpson-Holley et al, 2011; White and Lloyd, 2012). Consequently, it has been proposed that SGs function in part as antiviral defense granules to inhibit translation, block mitosis, and prime cells for apoptosis in response to cytoplasmic surges of viral factors, and that extant viruses have necessarily evolved mechanisms to evade this innate intracellular defense.…”

Ribosomal protein L22 inhibits regulation of cellular activities by the Epstein‐Barr virus small RNA EBER‐1

“…5A (lower panel, lanes 7 and 8). The latter figure also illustrates that L22 alone had no effect either on basal PKR activity (upper panel, lane 1 vs. lanes 3-5) or on the activation of the protein kinase by poly(I).poly(C) (lane 2 vs. lanes [6][7][8]. Figure 5B provides confirmation that the protein which is phosphorylated when recombinant L22 is added to assays containing active PKR is indeed the ribosomal protein itself.…”

A dynamically tuned double‐stranded RNA binding mechanism for the activation of antiviral kinase PKR

“…Indeed, PKR is known to recognize a variety of viral dsRNAs, including structured RNAs that contain only short segments of uninterrupted Watson–Crick base pairing, such as HIV‐Tar, adenovirus VAI RNA, EBV RNAs, EBER‐1 and EBER‐2, etc. (Clemens et al ., 1994). In fact, a more recent systematic study has documented that PKR can bind dsRNAs with secondary structure defects such as a GA:AG mismatch and non‐contiguous helix (Bevilacqua et al ., 1998).…”

Movements of HIV-1 genomic RNA-APOBEC3F complexes and PKR reveal cytoplasmic and nuclear PKR defenses and HIV-1 evasion strategies

“…Our conclusion that SG formation is PKR dependent and requires a suprathreshold concentration of cytoplasmic gRNA is compatible with evidence that cells contain endogenous PKR inhibitors including proteins with dsRBDs and inhibitory RNAs (Bannwarth and Gatignol, 2005; Brand et al, 1997; Cai et al, 2000; Clemens et al, 1994; Clerzius et al, 2009; Clerzius et al, 2011; Clerzius et al, 2013; Daher et al, 2009; Endo-Munoz et al, 2005; Ong et al, 2005; Samuel, 1992; Sanghvi and Steel, 2011; Singh et al, 2011). Those studies principally analyzed levels of PKR-P and other proteins in post-nuclear cytoplasmic extracts from whole cell cultures.…”

“…Many viruses have evolved mechanisms to suppress SGs by limiting synthesis and nuclear export of viral mRNAs and/or by inactivating factors needed for SG assembly or stability (Abrahamyan et al, 2010; Bannwarth and Gatignol, 2005; Brand et al, 1997; Cai et al, 2000; Clemens et al, 1994; Clerzius et al, 2011; Courtney et al, 2012; Emara and Brinton, 2007; Fros et al, 2012; Gordon et al, 2013; Kedersha and Anderson, 2007; McInerney et al, 2005; Montero et al, 2008; Nallagatla et al, 2011; Sanghvi and Steel, 2011; Simpson-Holley et al, 2011; White and Lloyd, 2012). Consequently, it has been proposed that SGs function in part as antiviral defense granules to inhibit translation, block mitosis, and prime cells for apoptosis in response to cytoplasmic surges of viral factors, and that extant viruses have necessarily evolved mechanisms to evade this innate intracellular defense.…”

Ribosomal protein L22 inhibits regulation of cellular activities by the Epstein‐Barr virus small RNA EBER‐1

“…5A (lower panel, lanes 7 and 8). The latter figure also illustrates that L22 alone had no effect either on basal PKR activity (upper panel, lane 1 vs. lanes 3-5) or on the activation of the protein kinase by poly(I).poly(C) (lane 2 vs. lanes [6][7][8]. Figure 5B provides confirmation that the protein which is phosphorylated when recombinant L22 is added to assays containing active PKR is indeed the ribosomal protein itself.…”

A dynamically tuned double‐stranded RNA binding mechanism for the activation of antiviral kinase PKR

“…Indeed, PKR is known to recognize a variety of viral dsRNAs, including structured RNAs that contain only short segments of uninterrupted Watson–Crick base pairing, such as HIV‐Tar, adenovirus VAI RNA, EBV RNAs, EBER‐1 and EBER‐2, etc. (Clemens et al ., 1994). In fact, a more recent systematic study has documented that PKR can bind dsRNAs with secondary structure defects such as a GA:AG mismatch and non‐contiguous helix (Bevilacqua et al ., 1998).…”