PMID- 27124581
OWN - NLM
STAT- MEDLINE
DCOM- 20161215
LR  - 20231213
IS  - 2041-4889 (Electronic)
VI  - 7
IP  - 4
DP  - 2016 Apr 28
TI  - The hnRNP-Htt axis regulates necrotic cell death induced by transcriptional 
      repression through impaired RNA splicing.
PG  - e2207
LID - 10.1038/cddis.2016.101 [doi]
AB  - In this study, we identify signaling network of necrotic cell death induced by 
      transcriptional repression (TRIAD) by alpha-amanitin (AMA), the selective RNA 
      polymerase II inhibitor, as a model of neurodegenerative cell death. We performed 
      genetic screen of a knockdown (KD) fly library by measuring the ratio of 
      transformation from pupa to larva (PL ratio) under TRIAD, and selected the cell 
      death-promoting genes. Systems biology analysis of the positive genes mapped on 
      protein-protein interaction databases predicted the signaling network of TRIAD 
      and the core pathway including heterogeneous nuclear ribonucleoproteins (hnRNPs) 
      and huntingtin (Htt). RNA sequencing revealed that AMA impaired transcription and 
      RNA splicing of Htt, which is known as an endoplasmic reticulum (ER)-stabilizing 
      molecule. The impairment in RNA splicing and PL ratio was rescued by 
      overexpresion of hnRNP that had been also affected by transcriptional repression. 
      Fly genetics with suppressor or expresser of Htt and hnRNP worsened or 
      ameliorated the decreased PL ratio by AMA, respectively. Collectively, these 
      results suggested involvement of RNA splicing and a regulatory role of the 
      hnRNP-Htt axis in the process of the transcriptional repression-induced necrosis.
FAU - Mao, Y
AU  - Mao Y
AD  - Department of Neuropathology, Medical Research Institute, Tokyo Medical and 
      Dental University, Bunkyo-ku, Tokyo, Japan.
FAU - Tamura, T
AU  - Tamura T
AD  - Department of Neuropathology, Medical Research Institute, Tokyo Medical and 
      Dental University, Bunkyo-ku, Tokyo, Japan.
FAU - Yuki, Y
AU  - Yuki Y
AD  - Department of Neuropathology, Medical Research Institute, Tokyo Medical and 
      Dental University, Bunkyo-ku, Tokyo, Japan.
FAU - Abe, D
AU  - Abe D
AD  - Department of Neuropathology, Medical Research Institute, Tokyo Medical and 
      Dental University, Bunkyo-ku, Tokyo, Japan.
FAU - Tamada, Y
AU  - Tamada Y
AD  - Department of Computer Science, Graduate School of Information Science and 
      Technology, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
FAU - Imoto, S
AU  - Imoto S
AD  - Laboratory of DNA Information Analysis, Human Genome Center, Institute of Medical 
      Science, The University of Tokyo, Minato-ku, Tokyo, Japan.
FAU - Tanaka, H
AU  - Tanaka H
AD  - Department of Neuropathology, Medical Research Institute, Tokyo Medical and 
      Dental University, Bunkyo-ku, Tokyo, Japan.
FAU - Homma, H
AU  - Homma H
AD  - Department of Neuropathology, Medical Research Institute, Tokyo Medical and 
      Dental University, Bunkyo-ku, Tokyo, Japan.
FAU - Tagawa, K
AU  - Tagawa K
AD  - Department of Neuropathology, Medical Research Institute, Tokyo Medical and 
      Dental University, Bunkyo-ku, Tokyo, Japan.
FAU - Miyano, S
AU  - Miyano S
AD  - Laboratory of DNA Information Analysis, Human Genome Center, Institute of Medical 
      Science, The University of Tokyo, Minato-ku, Tokyo, Japan.
FAU - Okazawa, H
AU  - Okazawa H
AD  - Department of Neuropathology, Medical Research Institute, Tokyo Medical and 
      Dental University, Bunkyo-ku, Tokyo, Japan.
AD  - Center for Brain Integration Research, Tokyo Medical and Dental University, 
      Bunkyo-ku, Tokyo, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160428
PL  - England
TA  - Cell Death Dis
JT  - Cell death & disease
JID - 101524092
RN  - 0 (Amanitins)
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Drosophila Proteins)
RN  - 0 (Heterogeneous-Nuclear Ribonucleoprotein Group A-B)
RN  - 0 (Heterogeneous-Nuclear Ribonucleoproteins)
RN  - 0 (Hnrnpab protein, rat)
RN  - 0 (Htt protein, Drosophila)
RN  - 0 (Huntingtin Protein)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Ribonucleoproteins)
RN  - 0 (Transcription Factors)
RN  - 0 (beta-Transducin Repeat-Containing Proteins)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
SB  - IM
MH  - Amanitins/pharmacology
MH  - Animals
MH  - *Apoptosis/drug effects
MH  - Cell Cycle Proteins/genetics/metabolism
MH  - Cells, Cultured
MH  - Drosophila/growth & development/metabolism
MH  - Drosophila Proteins/genetics/*metabolism
MH  - Embryo, Mammalian/cytology
MH  - Heterogeneous-Nuclear Ribonucleoprotein Group A-B/genetics/metabolism
MH  - Heterogeneous-Nuclear Ribonucleoproteins/genetics/*metabolism
MH  - Huntingtin Protein/antagonists & inhibitors/genetics/*metabolism
MH  - Larva/metabolism
MH  - Neurons/cytology/metabolism
MH  - Protein Serine-Threonine Kinases/genetics/metabolism
MH  - Proto-Oncogene Proteins/genetics/metabolism
MH  - Pupa/metabolism
MH  - RNA Splicing/drug effects
MH  - Rats
MH  - Rats, Wistar
MH  - Ribonucleoproteins/genetics/metabolism
MH  - Transcription Factors/genetics/metabolism
MH  - Transcription, Genetic/drug effects
MH  - beta-Transducin Repeat-Containing Proteins/genetics/metabolism
MH  - Polo-Like Kinase 1
PMC - PMC4855646
EDAT- 2016/04/29 06:00
MHDA- 2016/12/16 06:00
PMCR- 2016/04/01
CRDT- 2016/04/29 06:00
PHST- 2016/02/10 00:00 [received]
PHST- 2016/03/18 00:00 [revised]
PHST- 2016/03/21 00:00 [accepted]
PHST- 2016/04/29 06:00 [entrez]
PHST- 2016/04/29 06:00 [pubmed]
PHST- 2016/12/16 06:00 [medline]
PHST- 2016/04/01 00:00 [pmc-release]
AID - cddis2016101 [pii]
AID - 10.1038/cddis.2016.101 [doi]
PST - epublish
SO  - Cell Death Dis. 2016 Apr 28;7(4):e2207. doi: 10.1038/cddis.2016.101.