Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0017160 (
gastroenteritis
)
11,398
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
XBP1
is a stress-regulated transcription factor also involved in mammalian host defenses and innate immune response. Our investigation of
XBP1
RNA splicing during rotavirus infection revealed that an additional
XBP1
RNA (
XBP1es
) that corresponded to exon skipping in the
XBP1
pre-RNA is induced depending on the rotavirus strain used. We show that the translation product of
XBP1es
(XBP1es) has
trans
-activation properties similar to those of
XBP1
on ER stress response element (ERSE) containing promoters. Using monoreassortant between ES
+
("skipping") and ES
-
("nonskipping") strains of rotavirus, we show that gene 7 encoding the viral translation enhancer NSP3 is involved in this phenomenon and that exon skipping parallels the nuclear relocalization of cytoplasmic PABP. We further show, using recombinant rotaviruses carrying chimeric gene 7, that the ES
+
phenotype is linked to the eIF4G-binding domain of NSP3. Because the
XBP1
transcription factor is involved in stress and immunological responses, our results suggest an alternative way to activate
XBP1
upon viral infection or nuclear localization of PABP.
IMPORTANCE
Rotavirus is one of the most important pathogens causing severe
gastroenteritis
in young children worldwide. Here we show that infection with several rotavirus strains induces an alternative splicing of the RNA encoding the stressed-induced transcription factor
XBP1
. The genetic determinant of
XBP1
splicing is the viral RNA translation enhancer NSP3. Since
XBP1
is involved in cellular stress and immune responses and since the
XBP1
protein made from the alternatively spliced RNA is an active transcription factor, our observations raise the question of whether alternative splicing is a cellular response to rotavirus infection.
...
PMID:Rotavirus Infection Alters Splicing of the Stress-Related Transcription Factor XBP1. 3054 62
