TY - JOUR AB - Eukaryotic cells rely on the precise determination of when and where proteins are synthesized. Spatiotemporal expression is supported by localization of mRNAs to specific subcellular sites and their subsequent local translation. This holds true for somatic cells as well as for oocytes and embryos. Most commonly, mRNA localization is achieved by active transport of the molecules along the actin or microtubule cytoskeleton. Key factors are molecular motors, adaptors, and RNA-binding proteins that recognize defined sequences or structures in cargo mRNAs. A deep understanding of this process has been gained from research on fungal model systems such as Saccharomyces cerevisiae and Ustilago maydis. Recent highlights of these studies are the following: (1) synergistic binding of two RNA-binding proteins is needed for high affinity recognition; (2) RNA sequences undergo profound structural rearrangements upon recognition; (3) mRNA transport is tightly linked to membrane trafficking; (4) mRNAs and ribosomes are transported on the cytoplasmic surface of endosomes; and (5) heteromeric protein complexes are, most likely, assembled co-translationally during endosomal transport. Thus, the study of simple fungal model organisms provides valuable insights into fundamental mechanisms of mRNA transport boosting the understanding of similar events in higher eukaryotes. For further resources related to this article, please visit the WIREs website. AU - Niessing, D. AU - Jansen, R.P.* AU - Pohlmann, T* AU - Feldbrügge, M.* C1 - 52153 C2 - 43741 CY - Hoboken TI - mRNA transport in fungal top models. JO - Wiley Interdiscip. Rev. RNA VL - 9 IS - 1 PB - Wiley PY - 2017 SN - 1757-7004 ER - TY - JOUR AB - Posttranscriptional regulation of gene expression plays a central role in the initiation of innate and adaptive immune responses. This is exemplified by the protein Roquin, which has attracted great interest during the past decade owing to its ability to prevent autoimmunity. Roquin controls T-cell activation and T helper cell differentiation by limiting the induced expression of costimulatory receptors on the surface of T cells. It does so by recognizing cis regulatory RNA-hairpin elements in the 3' UTR of target transcripts via its ROQ domain-a novel RNA-binding fold-and triggering their degradation through recruitment of factors that mediate deadenylation and decapping. Recent structural studies have revealed molecular details of the recognition of RNA hairpin structures by the ROQ domain. Surprisingly, it was found that Roquin mainly relies on shape-specific recognition of the RNA. This observation implies that a much broader range of RNA motifs could interact with the protein, but it also complicates systematic searches for novel mRNA targets of Roquin. Thus, large-scale approaches, such as crosslinking and immunoprecipitation or systematic evolution of ligands by exponential enrichment experiments coupled with next-generation sequencing, will be required to identify the complete spectrum of its target RNAs. Together with structural analyses of their binding modes, this will enable us to unravel the intricate complexity of 3' UTR regulation by Roquin and other trans-acting factors. Here, we review our current understanding of Roquin-RNA interactions and their role for Roquin function. For further resources related to this article, please visit the WIREs website. AU - Schlundt, A. AU - Niessing, D. AU - Heissmeyer, V. AU - Sattler, M. C1 - 48012 C2 - 39844 CY - Hoboken SP - 455-469 TI - RNA recognition by Roquin in posttranscriptional gene regulation. JO - Wiley Interdiscip. Rev. RNA VL - 7 IS - 4 PB - Wiley-blackwell PY - 2016 SN - 1757-7004 ER - TY - JOUR AB - During the cell cycle the expression of replication-dependent histones is tightly coupled to DNA synthesis. Histone messenger RNA (mRNA) levels strongly increase during early S-phase and rapidly decrease at the end of it. Here, we review the degradation of replication-dependent histone mRNAs, a paradigm of post-transcriptional gene regulation, in the context of processing, translation, and oligouridylation. Replication-dependent histone transcripts are characterized by the absence of introns and by the presence of a stem-loop structure at the 3' end of a very short 3' untranslated region (UTR). These features, together with a need for active translation, are a prerequisite for their rapid decay. The degradation is induced by 3' end additions of untemplated uridines, performed by terminal uridyl transferases. Such 3' oligouridylated transcripts are preferentially bound by the heteroheptameric LSM1-7 complex, which also interacts with the 3'→5' exonuclease ERI1 (also called 3'hExo). Presumably in cooperation with LSM1-7 and aided by the helicase UPF1, ERI1 degrades through the stem-loop of oligouridylated histone mRNAs in repeated rounds of partial degradation and reoligouridylation. Although histone mRNA decay is now known in some detail, important questions remain open: How is ceasing nuclear DNA replication relayed to the cytoplasmic histone mRNA degradation? Why is translation important for this process? Recent research on factors such as SLIP1, DBP5, eIF3, CTIF, CBP80/20, and ERI1 has provided new insights into the 3' end formation, the nuclear export, and the translation of histone mRNAs. We discuss how these results fit with the preparation of histone mRNAs for degradation, which starts as early as these transcripts are generated. For further resources related to this article, please visit the WIREs website. Conflict of interest: The authors have declared no conflicts of interest for this article. AU - Höfig, K.P. AU - Heissmeyer, V. C1 - 30991 C2 - 34069 CY - Hoboken SP - 577-589 TI - Degradation of oligouridylated histone mRNAs: See UUUUU and goodbye. JO - Wiley Interdiscip. Rev. RNA VL - 5 IS - 4 PB - Wiley-blackwell PY - 2014 SN - 1757-7004 ER -