Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=28325765
&cmd=llinks): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 215
Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 298.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 298.79999999999995 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\28325765
.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 mBio
2017 ; 8
(2
): ä Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
Caenorhabditis elegans RIG-I Homolog Mediates Antiviral RNA Interference
Downstream of Dicer-Dependent Biogenesis of Viral Small Interfering RNAs
#MMPMID28325765
Coffman SR
; Lu J
; Guo X
; Zhong J
; Jiang H
; Broitman-Maduro G
; Li WX
; Lu R
; Maduro M
; Ding SW
mBio
2017[Mar]; 8
(2
): ä PMID28325765
show ga
Dicer enzymes process virus-specific double-stranded RNA (dsRNA) into small
interfering RNAs (siRNAs) to initiate specific antiviral defense by related RNA
interference (RNAi) pathways in plants, insects, nematodes, and mammals.
Antiviral RNAi in Caenorhabditis elegans requires Dicer-related helicase 1
(DRH-1), not found in plants and insects but highly homologous to mammalian
retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs), intracellular viral
RNA sensors that trigger innate immunity against RNA virus infection. However, it
remains unclear if DRH-1 acts analogously to initiate antiviral RNAi in
C. elegans Here, we performed a forward genetic screen to characterize antiviral
RNAi in C. elegans Using a mapping-by-sequencing strategy, we uncovered four
loss-of-function alleles of drh-1, three of which caused mutations in the
helicase and C-terminal domains conserved in RLRs. Deep sequencing of small RNAs
revealed an abundant population of Dicer-dependent virus-derived small
interfering RNAs (vsiRNAs) in drh-1 single and double mutant animals after
infection with Orsay virus, a positive-strand RNA virus. These findings provide
further genetic evidence for the antiviral function of DRH-1 and illustrate that
DRH-1 is not essential for the sensing and Dicer-mediated processing of the viral
dsRNA replicative intermediates. Interestingly, vsiRNAs produced by drh-1 mutants
were mapped overwhelmingly to the terminal regions of the viral genomic RNAs, in
contrast to random distribution of vsiRNA hot spots when DRH-1 is functional. As
RIG-I translocates on long dsRNA and DRH-1 exists in a complex with Dicer, we
propose that DRH-1 facilitates the biogenesis of vsiRNAs in nematodes by
catalyzing translocation of the Dicer complex on the viral long dsRNA
precursors.IMPORTANCE The helicase and C-terminal domains of mammalian RLRs sense
intracellular viral RNAs to initiate the interferon-regulated innate immunity
against RNA virus infection. Both of the domains from human RIG-I can substitute
for the corresponding domains of DRH-1 to mediate antiviral RNAi in C. elegans,
suggesting an analogous role for DRH-1 as an intracellular dsRNA sensor to
initiate antiviral RNAi. Here, we developed a forward genetic screen for the
identification of host factors required for antiviral RNAi in C. elegans
Characterization of four distinct drh-1 mutants obtained from the screen revealed
that DRH-1 did not function to initiate antiviral RNAi. We show that DRH-1 acted
in a downstream step to enhance Dicer-dependent biogenesis of viral siRNAs in
C. elegans As mammals produce Dicer-dependent viral siRNAs to target RNA viruses,
our findings suggest a possible role for mammalian RLRs and interferon signaling
in the biogenesis of viral siRNAs.
free
free
free
