scholarly journals Epigenetic Regulation of mRNA Polyadenylation Site Selection

2019 ◽  
Vol 180 (1) ◽  
pp. 7-9
Author(s):  
Lisa M. Smith
Keyword(s):  
Epigenetic Regulation ◽  
Site Selection ◽  
Polyadenylation Site ◽  
Mrna Polyadenylation

scholarly journals Use of Intron-Disrupted Polyadenylation Sites To Enhance Expression and Safety of Retroviral Vectors

2001 ◽  
Vol 75 (1) ◽  
pp. 199-204 ◽  
Author(s):  
Said I. Ismail ◽  
Jonathan B. Rohll ◽  
Susan M. Kingsman ◽  
Alan J. Kingsman ◽  
Mark Uden
Keyword(s):  
Site Selection ◽  
Expression Vector ◽  
Retroviral Vectors ◽  
Expression Vectors ◽  
Enhanced Expression ◽  
Producer Cell ◽  
Polyadenylation Sites ◽  
Internal Signal ◽  
Mrna Polyadenylation ◽  
Polyadenylation Signals

ABSTRACT Normal mRNA polyadenylation signals are composed of an AAUAAA motif and G/U box spaced 20 to 30 bp apart. If this spacing is increased further, then polyadenylation is disrupted. Previously it has been demonstrated that insertion of an intron will similarly disrupt this signal even though such introns are removed during a nuclear splicing reaction (X. Liu and J. Mertz, Nucleic Acids Res. 21:5256–5263, 1993). This observation has led to the suggestion that polyadenylation site selection is undertaken prior to intron excision. We now present results that both support and extend these observations and in doing so create a novel class of retroviral expression vector with improved qualities. We found that when an intron-disrupted polyadenylation signal is inserted within a retroviral expression vector, such a signal, although reformed in the producer cell, remains benign until transduction, where it is then preferentially used. Thus, we demonstrate that upon transduction these vectors now produce a majority of shortened subgenomic species and as a consequence have a reduced tendency for subsequent mobilization from transduced cells. In addition, we demonstrate that the use of this internal signal leads to enhanced expression from such vectors and that this is achieved without any loss in titer. Therefore, split polyadenylation signals confer enhanced performance and improved safety upon retroviral expression vectors into which they are inserted. Such split signals may prove useful for the future optimization of retroviral vectors in gene therapy.

scholarly journals Genome-Wide Analysis of MEF2 Transcriptional Program Reveals Synaptic Target Genes and Neuronal Activity-Dependent Polyadenylation Site Selection

Neuron ◽  
2008 ◽  
Vol 60 (6) ◽  
pp. 1022-1038 ◽  
Author(s):  
Steven W. Flavell ◽  
Tae-Kyung Kim ◽  
Jesse M. Gray ◽  
David A. Harmin ◽  
Martin Hemberg ◽  
...  
Keyword(s):  
Neuronal Activity ◽  
Site Selection ◽  
Target Genes ◽  
Polyadenylation Site ◽  
Transcriptional Program ◽  
Genome Wide Analysis ◽  
Genome Wide ◽  
Activity Dependent

Cell-specific expression of secreted versus membrane forms of immunoglobulin gamma 2b mRNA involves selective use of alternate polyadenylation sites

1985 ◽  
Vol 5 (10) ◽  
pp. 2514-2520
Author(s):  
C Milcarek ◽  
B Hall
Keyword(s):  
Heavy Chain ◽  
Plasma Cells ◽  
Single Gene ◽  
Polyadenylation Site ◽  
B Cell Differentiation ◽  
Specific Expression ◽  
Myeloma Cells ◽  
Isolated Nuclei ◽  
Mrna Polyadenylation ◽  
Alternate Polyadenylation

Immunoglobulin heavy chain genes encode at least two forms of mRNA, secretory- and membrane-specific. In less mature B cells and tumors arising from them, lymphomas, the membrane form of the protein and mRNA are in high abundance, while in more mature stages, plasma cells, and myeloma tumor cells, the secreted forms of protein and mRNA predominate. In myeloma cells producing approximately 8:1 ratios of secretory- to membrane-encoding forms of gamma-heavy chain mRNA, we observed equimolar transcription of the secretory- and membrane-encoding exons of the gene. In isolated nuclei from 4T001 (gamma 2b) and K23 (gamma 2a) myeloma cells, the secretory-encoding mRNA polyadenylation site was used at least three times as often as the membrane-encoding mRNA polyadenylation site. In the A20 (gamma 2a) lymphoma, which produces equal amounts of mature secretory- and membrane-encoding heavy chain mRNAs, results of experiments with isolated nuclei showed that the membrane mRNA polyadenylation site was used about two times as often as the secretory mRNA polyadenylation site. Selective use of alternate polyadenylation and cleavage sites, therefore, can modulate the production of the two mRNAs from a single gene during B cell differentiation.

scholarly journals Sequence determinants in human polyadenylation site selection

BMC Genomics ◽  
2003 ◽  
Vol 4 (1) ◽  
Author(s):  
Matthieu Legendre ◽  
Daniel Gautheret
Keyword(s):  
Site Selection ◽  
Polyadenylation Site

Properties of human liver cytosolic aspartate aminotransferase mRNAs generated by alternative polyadenylation site selection

Biochemistry ◽  
1990 ◽  
Vol 29 (22) ◽  
pp. 5293-5299 ◽  
Author(s):  
B. Bousquet-Lemercier ◽  
S. Pol ◽  
M. Pave-Preux ◽  
J. Hanoune ◽  
R. Barouki
Keyword(s):  
Site Selection ◽  
Aspartate Aminotransferase ◽  
Human Liver ◽  
Alternative Polyadenylation ◽  
Polyadenylation Site

scholarly journals Inference of the Human Polyadenylation Code

2017 ◽  
Author(s):  
Michael K. K. Leung ◽  
Andrew Delong ◽  
Brendan J. Frey
Keyword(s):  
Neural Network ◽  
Site Selection ◽  
Rna Binding ◽  
Genomic Sequence ◽  
Nucleosome Occupancy ◽  
Regulatory Elements ◽  
Polyadenylation Site ◽  
Tissue Specific ◽  
Protein Motifs ◽  
Polyadenylation Sites

AbstractProcessing of transcripts at the 3’-end involves cleavage at a polyadenylation site followed by the addition of a poly(A)-tail. By selecting which polyadenylation site is cleaved, alternative polyadenylation enables genes to produce transcript isoforms with different 3’-ends. To facilitate the identification and treatment of disease-causing mutations that affect polyadenylation and to understand the underlying regulatory processes, a computational model that can accurately predict polyadenylation patterns based on genomic features is desirable. Previous works have focused on identifying candidate polyadenylation sites and classifying sites which may be tissue-specific. What is lacking is a predictive model of the underlying mechanism of site selection, competition, and processing efficiency in a tissue-specific manner. We develop a deep learning model that trains on 3’-end sequencing data and predicts tissue-specific site selection among competing polyadenylation sites in the 3’ untranslated region of the human genome.Two neural network architectures are evaluated: one built on hand-engineered features, and another that directly learns from the genomic sequence. The hand-engineered features include polyadenylation signals, cis-regulatory elements, n-mer counts, nucleosome occupancy, and RNA-binding protein motifs. The direct-from-sequence model is inferred without prior knowledge on polyadenylation, based on a convolutional neural network trained with genomic sequences surrounding each polyadenylation site as input. Both models are trained using the TensorFlow library.The proposed polyadenylation code can predict site selection among competing polyadenylation sites in different tissues. Importantly, it does so without relying on evolutionary conservation. The model can distinguish pathogenic from benign variants that appear near annotated polyadenylation sites in ClinVar and inspect the genome to find candidate polyadenylation sites. We also provide an analysis on how different features affect the model’s performance.

scholarly journals Regulation of gene expression for translation initiation factor eIF-2α: importance of the 3′ untranslated region

1996 ◽  
Vol 315 (3) ◽  
pp. 791-798 ◽  
Author(s):  
Suzanne MIYAMOTO ◽  
John A. CHIORINI ◽  
Elena URCELAY ◽  
Brian SAFER
Keyword(s):  
Gene Expression ◽  
Site Selection ◽  
Untranslated Region ◽  
Regulation Of Gene Expression ◽  
Translation Initiation Factor ◽  
Polyadenylation Site ◽  
Initiation Factor ◽  
Activated T Cells ◽  
Α Subunit ◽  
Mouse Tissues

Gene expression of the α-subunit of eukaryotic initiation factor-2 (eIF-2α), involves transcriptional and post-transcriptional mechanisms. eIF-2α is a single-copy gene expressing two mRNAs, 1.6 and 4.2 kb in size. Cloning and sequencing of the cDNA for the 4.2 kb mRNA revealed that it is the result of alternative polyadenylation site selection. Four polyadenylation sites were identified within the 3´ untranslated region (UTR) of eIF-2α, only two of which are normally utilized in human and mouse tissues. A functional role for the extended 3´ UTR was assessed by comparing the translatability and stability of the 1.6 and 4.2 kb mRNAs. Both the 1.6 and 4.2 kb transcripts could be translated in vitro and were identified in vivo as being distributed on large polyribosomes. This indicates that both mRNAs are efficiently translated. Stability studies showed that in activated T-cells the 4.2 kb mRNA was more stable than the 1.6 kb mRNA. Polyadenylation site selection and mRNA stability differ for the two mRNAs of eIF-2α. These activities might be modulated by sequence elements contained within the untranslated regions of the eIF-2α gene.

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