PMID- 12730211
OWN - NLM
STAT- MEDLINE
DCOM- 20030827
LR  - 20210206
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 278
IP  - 29
DP  - 2003 Jul 18
TI  - Selective loss of trans-acting instability determinants of neurofilament mRNA in 
      amyotrophic lateral sclerosis spinal cord.
PG  - 26558-63
AB  - Neurofilament (NF) aggregates in motor neurons are a key neuropathological 
      feature of amyotrophic lateral sclerosis (ALS). We have previously observed an 
      alteration in the stoichiometry of NF subunit steady state mRNA levels in ALS 
      spinal motor neurons using in situ hybridization and proposed that this led to 
      aggregate formation. We have now examined the levels of NF mRNA in whole tissue 
      homogenates of spinal cord using the RNase protection assay and real time reverse 
      transcriptase-PCR and observed significant elevations of NF mRNA level in ALS. 
      Compared with age-matched control, we observed a greater stability of 
      heterogeneously expressed NFL mRNA in the presence of ALS spinal cord 
      homogenates. Heat denaturing or protease K digestion of the control homogenates 
      increased the stability of the NFL mRNA to levels observed in ALS homogenate. 
      Increased NFL mRNA stability was also induced by increasing the percentage of ALS 
      homogenate in an admixture of control and ALS homogenates. These observations 
      suggest the presence of trans-acting NFL mRNA-destabilizing elements in control 
      but not in ALS spinal cord homogenates. This was confirmed in gel retardation 
      assays. We also observed that the destabilizing elements interact with the 
      3'-untranslated region of NFL mRNA. These findings suggest that the trans-acting 
      NFL-destabilizing elements are selectively suppressed in ALS homogenates, 
      resulting in an increased stability and level of NFL mRNA.
FAU - Ge, Wei-Wen
AU  - Ge WW
AD  - Cell Biology Research Group, Robarts Research Institute, London, Ontario N6A 5K8, 
      Canada.
FAU - Leystra-Lantz, Cheryl
AU  - Leystra-Lantz C
FAU - Wen, Weiyan
AU  - Wen W
FAU - Strong, Michael J
AU  - Strong MJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20030501
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (3' Untranslated Regions)
RN  - 0 (Neurofilament Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (neurofilament protein L)
RN  - 9007-49-2 (DNA)
SB  - IM
MH  - 3' Untranslated Regions
MH  - Amyotrophic Lateral Sclerosis/*genetics/*metabolism
MH  - Base Sequence
MH  - Case-Control Studies
MH  - DNA/genetics
MH  - Humans
MH  - In Vitro Techniques
MH  - Motor Neurons/metabolism
MH  - Neurofilament Proteins/chemistry/*genetics/*metabolism
MH  - RNA Stability
MH  - RNA, Messenger/*genetics/*metabolism
MH  - Sequence Deletion
MH  - Spinal Cord/*metabolism
EDAT- 2003/05/06 05:00
MHDA- 2003/08/28 05:00
CRDT- 2003/05/06 05:00
PHST- 2003/05/06 05:00 [pubmed]
PHST- 2003/08/28 05:00 [medline]
PHST- 2003/05/06 05:00 [entrez]
AID - S0021-9258(20)84608-0 [pii]
AID - 10.1074/jbc.M302886200 [doi]
PST - ppublish
SO  - J Biol Chem. 2003 Jul 18;278(29):26558-63. doi: 10.1074/jbc.M302886200. Epub 2003 
      May 1.