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Cell cycle RNA regulons coordinating early lymphocyte development

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Lymphocytes undergo dynamic changes in gene expression as they develop from progenitor cells lacking antigen receptors, to mature cells that are prepared to mount immune responses. While transcription factors have established roles in lymphocyte development, they act in concert with post‐transcriptional and post‐translational regulators to determine the proteome. Furthermore, the post‐transcriptional regulation of RNA regulons consisting of mRNAs whose protein products act cooperatively allows RNA binding proteins to exert their effects at multiple points in a pathway. Here, we review recent evidence demonstrating the importance of RNA binding proteins that control the cell cycle in lymphocyte development and discuss the implications for tumorigenesis. WIREs RNA 2017, 8:e1419. doi: 10.1002/wrna.1419 This article is categorized under: RNA in Disease and Development > RNA in Disease RNA in Disease and Development > RNA in Development
Expression of mRNAs encoding RNA binding proteins in early lymphocyte development. Relative expression of selected mRNAs has been extracted from the immgen database. Source: http://www.immgen.org. Bars represent the mean, and error bars show the standard deviation of three measurements.
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mRNA structure and AU‐rich elements (AREs) within mouse mRNAs encoding factors involved in the G2‐M transition in the cell cycle. The proportion of each transcript that is 5′ UTR (blue), coding DNA sequence (CDS; red) and 3′ UTR (yellow) is shown. AREs in the 3′UTR with the sequence ‘WWAUUUAWW’ where W can be either U or A are marked with black symbols. Transcript information was downloaded from the Ensembl project of genome databases with BioMart software. Where genes were annotated with alternative UTRs or CDS, the longest sequence was selected.
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Regulation of the cell cycle by multiple targets of ZFP36L1/L2. ZFP36L1/L2 targets [deduced by AU‐rich element (ARE) sequences in the 3′UTR or by appearance in ZFP36L1 iCLIP] are shown. Proteins in blue had increased expression in Zfp36l1 Zfp36l2 KO lymphocytes (either mRNA or protein). P27 in yellow had decreased protein in Zfp36l1 Zfp36l2 KO lymphocytes. RB1 in gray was unchanged. Interactions between ZFP36L1/L2 targets allow them to cooperate to drive progression into the S phase of the cell cycle.
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Early stages of B and T lymphocyte development. Important processes during B and T cell development are shown, with the corresponding stages of development. Stages of T cell development are abbreviated to double negative (DN), double positive (DP), and single positive (SP). Briefly, progenitor B and T cells rearrange their IgH or Tcrβ loci respectively, undergo proliferative selection, then rearrange their Igκ/λ or Tcrα loci to form unique antigen receptors.
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mRNA structure and AU‐rich elements (AREs) within mouse mRNAs encoding factors involved in the G1‐S transition in the cell cycle. The proportion of each transcript that is 5′ UTR (blue), coding DNA sequence (CDS; red) and 3′ UTR (yellow) is shown. AREs in the 3’UTR with the sequence ‘WWAUUUAWW’ where W can be either U or A are marked with black symbols. Transcript information was downloaded from the Ensembl project of genome databases with BioMart software. Where genes were annotated with alternative UTRs or CDS, the longest sequence was selected.
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