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Series GSE38907 Query DataSets for GSE38907
Status Public on Jun 25, 2013
Title KSRP-mediated Transcriptome reshaping
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary KSRP knock-down and BMP2 treatment produce a largely overlapping reshape of the transcriptome in C2C12 cells. microRNAs (miRNAs) are essential regulators of development, physiology, and evolution with miRNA biogenesis being strictly controlled at multiple levels. Regulatory proteins, such as KH-type splicing regulatory protein (KSRP), modulate rates and timing of the enzymatic reactions responsible for maturation of select miRNAs from their primary transcripts in response to specific stimuli. Induction of myogenic miRNAs (myomiRs) is essential for muscle differentiation with KSRP phosphorylation being required to convey myogenic signals to enhanced myomiR maturation. Here we show that either KSRP silencing or Bone Morphogenetic Protein (BMP)2-signaling activation in mesenchimal C2C12 cells prevented myogenic differentiation while induced osteoblastic differentiation as revealed by the reshaping of the whole transcriptome analyzed by RNA deep-sequencing. The most striking feature common to both BMP2 signaling activation and KSRP silencing was a blockade of myomiR maturation. Our results demonstrate that phosphorylated SMAD proteins, the transducers of BMP signaling, associate with KSRP and block its interaction with primary-myomiRs. This, in turn, abrogates KSRP-dependent myomiR maturation with the knock-down of SMAD4, 5, and 9 being able to rescue KSRP function. SMAD-induced blockade of KSRP-dependent myomiR maturation, in parallel to the well known SMAD function on gene transcription, inhibits C2C12 cell differentiation into myofibers and contributes to orient cells towards osteoblast lineage. We propose that remodeling of co-regulatory complexes affecting primary-miRNA processing is a mechanism well suited to guide cell fate determination in eukaryotes.
Overall design Total RNA was prepared from 1. untreated mock-transfected C2C12 cells; 2. BMP2-treated mock-transfected C2C12 cells; 3. untreated shKSRP-transfected C2C12 cells and analyzed by RNA-seq
Contributor(s) Pasero M, Giovarelli M, Bucci G, Gherzi R, Briata P
Citation(s) 23177623
Submission date Jun 25, 2012
Last update date May 15, 2019
Contact name Gabriele Bucci
Organization name Università vita e Salute Ospedale San Raffaele
Department Center of Translational Genomics and Bioinformatics
Street address Via Olgettina 60
City Milan
ZIP/Postal code 20132
Country Italy
Platforms (1)
GPL13112 Illumina HiSeq 2000 (Mus musculus)
Samples (3)
GSM951984 mock-GM
GSM951985 shKSRP-GM
GSM951986 mock-DM+BMP2
BioProject PRJNA169319
SRA SRP013888

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Supplementary file Size Download File type/resource
GSE38907_RAW.tar 16.7 Mb (http)(custom) TAR (of GTF)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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