• Molecules and Cells
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• 제39권4호
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• pp.281-285
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• 2016

Almost all of eukaryotic mRNAs are subjected to polyadenylation during mRNA processing. Recent discoveries showed that many of these mRNAs contain more than one polyadenylation sites in their 3' untranslated regions (UTR) and that alternative polyadenylation (APA) is prevalent among these genes. Many biological processes such as differentiation, proliferation, and tumorigenesis have been correlated to global APA events in the 3' UTR of mRNAs, suggesting that these APA events are tightly regulated and may play important physiological roles. In this review, recent discoveries in the physiological roles of APA events, as well as the known and proposed mechanisms are summarized. Perspective for future directions is also discussed.

• Molecules and Cells
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• 제46권1호
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• pp.57-64
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• 2023

In eukaryotic cells, a key RNA processing step to generate mature mRNA is the coupled reaction for cleavage and polyadenylation (CPA) at the 3' end of individual transcripts. Many transcripts are alternatively polyadenylated (APA) to produce mRNAs with different 3' ends that may either alter protein coding sequence (CDS-APA) or create different lengths of 3'UTR (tandem-APA). As the CPA reaction is intimately associated with transcriptional termination, it has been widely assumed that APA is regulated cotranscriptionally. Isoforms terminated at different regions may have distinct RNA stability under different conditions, thus altering the ratio of APA isoforms. Such differential impacts on different isoforms have been considered as post-transcriptional APA, but strictly speaking, this can only be considered "apparent" APA, as the choice is not made during the CPA reaction. Interestingly, a recent study reveals sequential APA as a new mechanism for post-transcriptional APA. This minireview will focus on this new mechanism to provide insights into various documented regulatory paradigms.

• Genomics & Informatics
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• 제5권4호
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• pp.174-178
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• 2007

The earliest stages of mammalian embryogenesis are governed by the activity of maternally inherited transcripts and proteins. Cytoplasmic polyadenylation of selected maternal mRNA has been reported to be a major control mechanism of delayed translation during preimplantation embryogenesis in mice. The presence of cis-elements required for cytoplasmic polyadenylation (e.g., CPE) can serve as a useful tag in the screening of maternal genes partaking in key functions in the transcriptionally dormant egg and early embryo. However, due to its relative simplicity, UA-rich sequences satisfying the canonical rule of known CPE consensus sequences are often found in the 3'-UTR of maternal transcripts that do not actually undergo cytoplasmic polyadenylation. In this study, we developed a method to confirm the validity of candidate CPE sequences in a given gene by a multiplex comparison of 3'-UTR sequences between mammalian homologs. We found that genes undergoing cytoplasmic polyadenylation tend to create a conserved block around the CPE, while CPE-like sequences in the 3'-UTR of genes lacking cytoplasmic polyadenylation do not exhibit such conservation between species. Through this cross-species comparison, we also identified an alternative CPE in the 3'-UTR of tissue-type plasminogen activator (tPA), which is more likely to serve as a functional element. We suggest that verification of CPEs based on sequence conservation can provide a convenient tool for mass screening of factors governing the earliest processes of mammalian embryogenesis.

• BMB Reports
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• 제50권4호
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• pp.201-207
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• 2017

Alternations in usage of polyadenylation sites during transcription termination yield transcript isoforms from a gene. Recent findings of transcriptome-wide alternative polyadenylation (APA) as a molecular response to changes in biology position APA not only as a molecular event of early transcriptional termination but also as a cellular regulatory step affecting various biological pathways. With the development of high-throughput profiling technologies at a single nucleotide level and their applications targeted to the 3'-end of mRNAs, dynamics in the landscape of mRNA 3'-end is measureable at a global scale. In this review, methods and technologies that have been adopted to study APA events are discussed. In addition, various bioinformatics algorithms for APA isoform analysis using publicly available RNA-seq datasets are introduced.

• Biomolecules & Therapeutics
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• 제14권2호
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• pp.75-82
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• 2006

Synaptic plasticity, which is a long lasting change in synaptic efficacy, underlies many neural processes like learning and memory. It has long been acknowledged that new protein synthesis is essential for both the expression of synaptic plasticity and memory formation and storage. Most of the research interests in this field have focused on the events regulating transcriptional activation of gene expression from the cell body and nucleus. Considering extremely differentiated structural feature of a neuron in CNS, a neuron should meet a formidable task to overcome spatial and temporal restraints to deliver newly synthesized proteins to specific activated synapses among thousands of others, which are sometimes several millimeters away from the cell body. Recent advances in synaptic neurobiology has found that almost all the machinery required for the new protein translation are localized inside or at least in the vicinity of postsynaptic compartments. These findings led to the hypothesis that dormant mRNAs are translationally activated locally at the activated synapse, which may enable rapid and delicate control of new protein synthesis at activated synapses. In this review, we will describe the mechanism of local translational control at activated synapses focusing on the role of cytoplasmic polyadenylation of dormant mRNAs.

• Molecules and Cells
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• 제37권9호
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• pp.644-649
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• 2014

The 3' ends of most eukaryotic messenger RNAs must undergo a maturation step that includes an endonuc-leolytic cleavage followed by addition of a polyadenylate tail. While this reaction is catalyzed by the action of only two enzymes it is supported by an unexpectedly large number of proteins. This complexity reflects the necessity of coordinating this process with other nuclear events, and growing evidence indicates that even more factors than previously thought are necessary to connect 3' processing to additional cellular pathways. In this review we summarize the current understanding of the molecular machinery involved in this step of mRNA maturation, focusing on new core and auxiliary proteins that connect polyadenylation to splicing, DNA damage, transcription and cancer.

• Animal cells and systems
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• 제3권4호
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• pp.413-415
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• 1999

Our previous report demonstrated that the rhp51$^＋$, a recA and RAD51 homolog of the fission yeast, encodes three transcripts of 1.9, 1.6 and 1.3 kb which have at least six polyadenylation sites. The 3'-end of the gene alone can direct the formation of multiple, discrete 3'ends of the transcripts. To identify the regulatory element required for the 3'-end formation of -rhp51$^＋$ deletion mapping analysis was performed. Northern blot analysis revealed that the 254-bp DNA fragment including 4 distinct poly (A) sites downstream from the Hindlll site, is crucial for normal 3'-end formation. Deletion of the 3'-terminal AU rich region caused appearance of read-through RNA, leading to enhancement of survival rate of the rhp51 deletion mutant in response to DNA damaging agent, methylmethane sulfonate (MMS). The results imply that the rhp51$^＋$ system may be useful for molecular analysis of the 3'-end formation of RNA in the fission yeast.

• Molecules and Cells
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• 제46권1호
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• pp.48-56
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• 2023

Genomic information stored in the DNA is transcribed to the mRNA and translated to proteins. The 3' untranslated regions (3'UTRs) of the mRNA serve pivotal roles in post-transcriptional gene expression, regulating mRNA stability, translation, and localization. Similar to DNA mutations producing aberrant proteins, RNA alterations expand the transcriptome landscape and change the cellular proteome. Recent global analyses reveal that many genes express various forms of altered RNAs, including 3'UTR length variants. Alternative polyadenylation and alternative splicing are involved in diversifying 3'UTRs, which could act as a hidden layer of eukaryotic gene expression control. In this review, we summarize the functions and regulations of 3'UTRs and elaborate on the generation and functional consequences of 3'UTR diversity. Given that dynamic 3'UTR length control contributes to phenotypic complexity, dysregulated 3'UTR diversity might be relevant to disease development, including cancers. Thus, 3'UTR diversity in cancer could open exciting new research areas and provide avenues for novel cancer theragnostics.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 2006년도 Spring Conference
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• pp.21-30
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• 2006

• 한국약용작물학회:학술대회논문집
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• 한국약용작물학회 2006년도 Spring Conference
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• pp.19-30
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• 2006