Control of the heat stress‐induced alternative splicing of a subset of genes by hnRNP K

Yamamoto, Kōichi; Furukawa, Masao; Fukumura, Kazuhiro; Kawamura, Arisa; Yamada, Tomoko; Suzuki, Hitoshi; Hirose, Tetsuro; Sakamoto, Hiroshi; Inoue, Kimiko

doi:10.1111/gtc.12400

Cited by 26 publications

(23 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, we also examined the levels of the DNAJB9 mRNA, another intron-retaining RNA that harbors a single HSATIII target intron ( Fig EV2A), and found that intron retention was detectable in control cells but not HSATIII KD cells ( Fig EV2B). We also confirmed that the thermal stress-responsive alternative splicing of the HSP105 and TNRC6a mRNAs reported previously (Yasuda et al, 1995;Yamamoto et al, 2016) was barely affected by HSATIII knockdown (Fig EV2C), indicating selectivity of target pre-mRNAs by HSATIII lncRNAs.…”

Section: Hsatiii Affects the Kinetics Of Accumulation Of Intron-retaisupporting

confidence: 92%

Lnc RNA ‐dependent nuclear stress bodies promote intron retention through SR protein phosphorylation

et al. 2019

Self Cite

View full text Add to dashboard Cite

A number of long noncoding RNAs (lncRNAs) are induced in response to specific stresses to construct membrane-less nuclear bodies; however, their function remains poorly understood. Here, we report the role of nuclear stress bodies (nSBs) formed on highly repetitive satellite III (HSATIII) lncRNAs derived from primate-specific satellite III repeats upon thermal stress exposure. A transcriptomic analysis revealed that depletion of HSATIII lncRNAs, resulting in elimination of nSBs, promoted splicing of 533 retained introns during thermal stress recovery. A HSATIII-Comprehensive identification of RNAbinding proteins by mass spectrometry (ChIRP-MS) analysis identified multiple splicing factors in nSBs, including serine and argininerich pre-mRNA splicing factors (SRSFs), the phosphorylation states of which affect splicing patterns. SRSFs are rapidly de-phosphorylated upon thermal stress exposure. During stress recovery, CDC like kinase 1 (CLK1) was recruited to nSBs and accelerated the re-phosphorylation of SRSF9, thereby promoting target intron retention. Our findings suggest that HSATIII-dependent nSBs serve as a conditional platform for phosphorylation of SRSFs by CLK1 to promote the rapid adaptation of gene expression through intron retention following thermal stress exposure.

show abstract

Section: Hsatiii Affects the Kinetics Of Accumulation Of Intron-retaisupporting

confidence: 92%

Lnc RNA ‐dependent nuclear stress bodies promote intron retention through SR protein phosphorylation

et al. 2019

Self Cite

View full text Add to dashboard Cite

show abstract

“…In addition, we also examined the levels of the DNAJB9 mRNA, another intron-retaining RNA that harbors a single HSATIII target intron ( Figure EV1A), and found that intron retention was detectable in control cells but not HSATIII cells ( Figure EV1B). We also confirmed that the thermal stress-responsive alternative splicing of the HSP105 and TNRC6a mRNAs reported previously (Yamamoto, Furukawa et al, 2016, Yasuda, Nakai et al, 1995 was barely affected by HSATIII knockdown ( Figure EV1C), indicating selectivity of target pre-mRNAs by HSATIII lncRNAs.…”

Section: Hsatiii Affects the Kinetics Of Accumulation Of Intron-retaisupporting

confidence: 91%

LncRNA-dependent nuclear stress bodies promote intron retention through SR protein phosphorylation

Ninomiya

Adachi

Natsume

et al. 2019

Preprint

Self Cite

View full text Add to dashboard Cite

A number of long noncoding RNAs (lncRNAs) are induced in response to specific stresses to construct membrane‐less nuclear bodies; however, their function remains poorly understood. Here, we report the role of nuclear stress bodies (nSBs) formed on highly repetitive satellite III (HSATIII) lncRNAs derived from primate‐specific satellite III repeats upon thermal stress exposure. A transcriptomic analysis revealed that depletion of HSATIII lncRNAs, resulting in elimination of nSBs, promoted splicing of 533 retained introns during thermal stress recovery. A HSATIII‐Comprehensive identification of RNA‐binding proteins by mass spectrometry (ChIRP‐MS) analysis identified multiple splicing factors in nSBs, including serine and arginine‐rich pre‐mRNA splicing factors (SRSFs), the phosphorylation states of which affect splicing patterns. SRSFs are rapidly de‐phosphorylated upon thermal stress exposure. During stress recovery, CDC like kinase 1 (CLK1) was recruited to nSBs and accelerated the re‐phosphorylation of SRSF9, thereby promoting target intron retention. Our findings suggest that HSATIII‐dependent nSBs serve as a conditional platform for phosphorylation of SRSFs by CLK1 to promote the rapid adaptation of gene expression through intron retention following thermal stress exposure.

show abstract

“…As shown in Additional file 8 : Fig. S2A, a significant downregulation was confirmed for the stress responsive splicing factor Srsf10 [ 67 ], while significant upregulations were observed for the cerebellar mRNA levels of Creb3 (human LZIP, synonymous LUMAN), which influences endoplasmic reticulum protein processing [ 68 , 69 ], and for Nfkbia (NF-Kappa-B inhibitor alpha), which cooperates with Creb3 to modulate the nuclear control of stress and inflammation responses [ 70 – 73 ], but not for other candidates within the Mapk (MAP kinase) gene family (Additional file 8 : Fig. S2A).…”

Section: Resultsmentioning

confidence: 94%

Progression of pathology in PINK1-deficient mouse brain from splicing via ubiquitination, ER stress, and mitophagy changes to neuroinflammation

Torres-Odio¹,

Key²,

Hoepken³

et al. 2017

J Neuroinflammation

View full text Add to dashboard Cite

BackgroundPINK1 deficiency causes the autosomal recessive PARK6 variant of Parkinson’s disease. PINK1 activates ubiquitin by phosphorylation and cooperates with the downstream ubiquitin ligase PARKIN, to exert quality control and control autophagic degradation of mitochondria and of misfolded proteins in all cell types.MethodsGlobal transcriptome profiling of mouse brain and neuron cultures were assessed in protein-protein interaction diagrams and by pathway enrichment algorithms. Validation by quantitative reverse transcriptase polymerase chain reaction and immunoblots was performed, including human neuroblastoma cells and patient primary skin fibroblasts.ResultsIn a first approach, we documented Pink1-deleted mice across the lifespan regarding brain mRNAs. The expression changes were always subtle, consistently affecting “intracellular membrane-bounded organelles”. Significant anomalies involved about 250 factors at age 6 weeks, 1300 at 6 months, and more than 3500 at age 18 months in the cerebellar tissue, including Srsf10, Ube3a, Mapk8, Creb3, and Nfkbia. Initially, mildly significant pathway enrichment for the spliceosome was apparent. Later, highly significant networks of ubiquitin-mediated proteolysis and endoplasmic reticulum protein processing occurred. Finally, an enrichment of neuroinflammation factors appeared, together with profiles of bacterial invasion and MAPK signaling changes—while mitophagy had minor significance. Immunohistochemistry showed pronounced cellular response of Iba1-positive microglia and GFAP-positive astrocytes; brain lipidomics observed increases of ceramides as neuroinflammatory signs at old age.In a second approach, we assessed PINK1 deficiency in the presence of a stressor. Marked dysregulations of microbial defense factors Ifit3 and Rsad2 were consistently observed upon five analyses: (1) Pink1 −/− primary neurons in the first weeks after brain dissociation, (2) aged Pink1 −/− midbrain with transgenic A53T-alpha-synuclein overexpression, (3) human neuroblastoma cells with PINK1-knockdown and murine Pink1 −/− embryonal fibroblasts undergoing acute starvation, (4) triggering mitophagy in these cells with trifluoromethoxy carbonylcyanide phenylhydrazone (FCCP), and (5) subjecting them to pathogenic RNA-analogue poly(I:C). The stress regulation of MAVS, RSAD2, DDX58, IFIT3, IFIT1, and LRRK2 was PINK1 dependent. Dysregulation of some innate immunity genes was also found in skin fibroblast cells from PARK6 patients.ConclusionsThus, an individual biomarker with expression correlating to progression was not identified. Instead, more advanced disease stages involved additional pathways. Hence, our results identify PINK1 deficiency as an early modulator of innate immunity in neurons, which precedes late stages of neuroinflammation during alpha-synuclein spreading.Electronic supplementary materialThe online version of this article (doi:10.1186/s12974-017-0928-0) contains supplementary material, which is available to authorized users.

show abstract

Control of the heat stress‐induced alternative splicing of a subset of genes by hnRNP K

Cited by 26 publications

References 25 publications

Lnc RNA ‐dependent nuclear stress bodies promote intron retention through SR protein phosphorylation

Lnc RNA ‐dependent nuclear stress bodies promote intron retention through SR protein phosphorylation

LncRNA-dependent nuclear stress bodies promote intron retention through SR protein phosphorylation

Progression of pathology in PINK1-deficient mouse brain from splicing via ubiquitination, ER stress, and mitophagy changes to neuroinflammation

Contact Info

Product

Resources

About