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The role of SON in splicing, development, and disease

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SON is a nuclear protein involved in multiple cellular processes including transcription, pre‐messenger RNA (mRNA) splicing, and cell cycle regulation. Although SON was discovered 25 years ago, the importance of SON's function was only realized recently when its roles in nuclear organization and pre‐mRNA splicing as well as the influence of these activities in maintaining cellular health were unveiled. Furthermore, SON was implicated to have a key role in stem cells as well as during the onset of various diseases such as cancer, influenza, and hepatitis. Here we review the progress that has been made in studying this multifunctional protein and discuss questions that remain to be answered about SON. WIREs RNA 2014, 5:637–646. doi: 10.1002/wrna.1235 This article is categorized under: RNA Processing > Splicing Mechanisms

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A model for SON as a multifunctional scaffold. (a) SON organizes nuclear speckle components through its repetitive domains while the C‐terminus of SON including the G‐patch is required for its interaction with the nuclear‐retained long noncoding RNA MALAT1 (metastasis‐associated lung adenocarcinoma transcript 1). Expression and distribution of components impacts the overall subnuclear organization of RNA processing factors. DNA is stained by Hoechst in blue and SON is stained red to mark nuclear speckles. (b) SON and MALAT1 recruit serine/arginine‐rich (SR) proteins to mediate co‐transcriptional splicing of sub‐optimal splice sites and alternative splicing of exons. Son may remain associated with mature mRNPs. CTD: c‐terminal domain of RNA polymerase II. *Represents weak/dual‐specificity splice sites.
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SON localization throughout the cell cycle. SON colocalizes with splicing factor SRSF1 in HeLa cells throughout the cell cycle. Immunofluorescence localization of SON and of SRSF1 shows colocalization as well as reorganization of cellular distribution of these splicing factors during mitosis. Specific localization is observed in mitotic interchromatin granules (MIGs; arrow) during mitosis. DNA was stained with DAPI. Panels in order from left to right: interphase, prophase (before nuclear envelope breakdown, prophase (after nuclear envelope breakdown), metaphase, anaphase, telophase, and G1. Bar = 5 µm. Images provided by Keshia Torres‐Munoz and Paula Bubulya.
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SON regulates gene expression in stem cells. (a) SON promotes intron removal from human embryonic stem cell (hESC) maintenance and survival genes. (b) SON facilitates correct isoform expression of hESC specific genes. (c) SON may directly or indirectly inhibit expression of miR23a‐27a‐24‐2 cluster to repress GATA2 expression in HSCs_ENREF_39. SON may interact with other factor to directly inhibit transcription of miR23a‐27a‐24‐2 cluster or act indirectly through regulating splicing of other factors responsible for miR23a‐27a‐24‐2 expression.
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