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Sequence Determinants As Key Regulators in Gene Expression of T Cells

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Journal Immunol Rev
Date 2021 Sep 6
PMID 34486113
Citations 7
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Abstract

T cell homeostasis, T cell differentiation, and T cell effector function rely on the constant fine-tuning of gene expression. To alter the T cell state, substantial remodeling of the proteome is required. This remodeling depends on the intricate interplay of regulatory mechanisms, including post-transcriptional gene regulation. In this review, we discuss how the sequence of a transcript influences these post-transcriptional events. In particular, we review how sequence determinants such as sequence conservation, GC content, and chemical modifications define the levels of the mRNA and the protein in a T cell. We describe the effect of different forms of alternative splicing on mRNA expression and protein production, and their effect on subcellular localization. In addition, we discuss the role of sequences and structures as binding hubs for miRNAs and RNA-binding proteins in T cells. The review thus highlights how the intimate interplay of post-transcriptional mechanisms dictate cellular fate decisions in T cells.

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References
1.
Ban Y, Oh S, Seo S, Kim S, Choi I, Greenberg P . miR-150-Mediated Foxo1 Regulation Programs CD8 T Cell Differentiation. Cell Rep. 2017; 20(11):2598-2611. DOI: 10.1016/j.celrep.2017.08.065. View

2.
Ramgolam V, DeGregorio S, Rao G, Collinge M, Subaran S, Markovic-Plese S . T cell LFA-1 engagement induces HuR-dependent cytokine mRNA stabilization through a Vav-1, Rac1/2, p38MAPK and MKK3 signaling cascade. PLoS One. 2011; 5(12):e14450. PMC: 3012057. DOI: 10.1371/journal.pone.0014450. View

3.
Ullrich S, Guigo R . Dynamic changes in intron retention are tightly associated with regulation of splicing factors and proliferative activity during B-cell development. Nucleic Acids Res. 2019; 48(3):1327-1340. PMC: 7026658. DOI: 10.1093/nar/gkz1180. View

4.
Mateju D, Eichenberger B, Voigt F, Eglinger J, Roth G, Chao J . Single-Molecule Imaging Reveals Translation of mRNAs Localized to Stress Granules. Cell. 2020; 183(7):1801-1812.e13. DOI: 10.1016/j.cell.2020.11.010. View

5.
Bugaut A, Balasubramanian S . 5'-UTR RNA G-quadruplexes: translation regulation and targeting. Nucleic Acids Res. 2012; 40(11):4727-41. PMC: 3367173. DOI: 10.1093/nar/gks068. View