31 - RNA Processing; Transport from Nucleus & tRNA and rRNA Processing

31 - RNA Processing; Transport from Nucleus & tRNA and rRNA Processing

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1 Control of gene expression: overall Transcription initiation •Direct influence of A and R on initiation •Chromatin remodeling and histone modifications •Methylation •Hormones and other “external” signals RNA processing •Alternative splicing and trans-splicing •polyadenylation Transport through the nuclear pore Posttranscriptional / pretranslational control (events on/with mRNA before ribosomes) •Localization of mRNA •RNA editing •Post-transcriptional silencing by siRNA or miRNA •Translational control switch •RNA stability (degradation and stabilization) Translational control (mRNA/ribosomes) •Phosphorylation of translation initiation factors •Upstream AUG codons •IRES Protein activity control •Posttranslational modification and transport Alberts, 4 th edition
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2 -prokaryotic mRNAs - half-lives are all in the range of 1-5 minutes, -eukaryotic mRNAs can vary greatly in their stability The balance between mRNA degradation and synthesis determines the level of individual mRNAs in cells -new finding (last few years) - presence of stabilizing elements in mRNA in 3’ UTR (IRE in transferrin receptor 3’UTR could be seen as one) but in coding sequence as well Pre-translational control: 5. mRNA longevity (stability)
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3 •Unstable transcripts have sequences (predominately, but not exclusively, in the 3'-non-translated regions) signals for rapid degradation - instability elements •Short lived mRNAs in eukaryotes have copies of “ AUUUA ” (called ARE= A U r ich e lement) in 3’ UTR •Degradation rate of mRNAs can be regulated by interaction with multiple specific RNA binding proteins (ARE-BP) •Different binding proteins for stabilization AND degradation (possible involvement of miRNAs ) •If degradation –could go from both 3’ and 5’ end due to presence of specific ARE-BP •These proteins can also determine the accessibility of the transcript by ribosomes Journal of Biomedicine and Biotechnology Volume 2009 (2009), Article ID 634520 [See: Cellular Oncology (2007), 29(1), pg. 117]
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4 Cellular Oncology (2007), 29(1), pg. 117 3UTR determinants and their alterations in cancer. (A) Schematic of the different regions in the mRNA. The 3UTR is enlarged to show the cis -elements (AREs, IREs and secondary structures) that are found in this region and the trans -acting factors (RNA-binding proteins and non-coding RNAs) that associate to them. (B) In cancer cells, two main groups of aberrant 3UTR regulation can be found: (1) Genetic alterations in cis -elements such as mutations, deletions, translocations and polymorphisms and (2) Altered levels of trans -acting factors (e.g.increase of ARE-BPs and decrease miRNAs levels), changes in their subcellular localization (e.g. increased cytoplasmic levels of ARE-BPs)
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31 - RNA Processing; Transport from Nucleus & tRNA and rRNA Processing

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