Suppressed RNA-Polymerase 1 Pathway Is Associated with Benign Multiple Sclerosis

• DOI: 10.1371/journal.pone.0046871
• Publication Date: 2012-10-12T21:39:05Z
• Authors: Anat Achiron; Anna Feldman; David Magalashvili; Mark Dolev; Michael Gurevich
• Keywords: Gene signature; Fold change

Benign multiple sclerosis (BMS) occurs in about 15% of patients with relapsing-remitting (RRMS) that over time do not develop significant neurological disability. The molecular events associated BMS are clearly understood. This study sought to underlie the biological mechanisms BMS. Blood samples obtained from a cohort 31 and 36 RRMS were applied for gene expression microarray analysis using HG-U133A-2 array (Affymetrix). Data analyzed by Partek pathway reconstruction was performed Ingenuity most informative genes (MIGs). We identified differing signature 406 MIGs between patients, mean±SE age 44.5±1.5 years, 24 females, 7 males, EDSS 1.9±0.2, disease duration 17.0±1.3 40.3±1.8 12 3.5±0.2, 10.9±1.4 years. enriched related RNA polymerase I (POL-1) transcription, general inflammatory response activation cell death. under-expressed operating POL-1 (p = 4.0*10−5) known while suppressed activate P53 dependent apoptosis suppress NFκB induced inflammation. In accordance, 30 target presented within signature, 19 had direction consistent activation. transcripts include transcription factor 3 (RRN3, p 4.8*10−5), polypeptide D (POLR1D, 2.2*10−4), leucine-rich PPR-motif containing protein (LRPPRC 2.3*10−5), followed suppression downstream family ribosomal like RPL3, 6,13,22 RPS6. accordance transcript release PTRF terminates over-expressed 4.4*10−3). Verification key confirmed qRT-PCR, RRN3 silencing resulted increase level PBMC sub-populations patients. Our findings demonstrate induce low activity