Functional Equivalence of an Evolutionarily Conserved RNA Binding Module

Wells, Melissa L.; Hicks, Stephanie; Perera, Lalith; Blackshear, Perry J.

doi:10.1074/jbc.m115.673012

Cited by 15 publications

(20 citation statements)

References 26 publications

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“…We used this change as a “diagnostic” indicator of ZFP36L3 because a leucine is present at this position in all mammalian family members other than ZFP36L3 that we have examined to date. Although we have not observed a proline residue in this position in any mammalian family members other than ZFP36L3, a proline at this site is found in some family member proteins from fungi (see, for example, (Wells, et al 2015)). Direct examination has shown that introducing the L to P modification into human TTP does not change its ability to interact with RNA (Lai, et al 2014).…”

Section: Discussioncontrasting

confidence: 57%

Emergence and evolution of Zfp36l3

Gingerich

Stumpo

Lai

et al. 2016

Molecular Phylogenetics and Evolution

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In most mammals, the Zfp36 gene family consists of three conserved members, with a fourth member, Zfp36l3, present only in rodents. The ZFP36 proteins regulate post-transcriptional gene expression at the level of mRNA stability in organisms from humans to yeasts, and appear to be expressed in all major groups of eukaryotes. In Mus musculus, Zfp36l3 expression is limited to the placenta and yolk sac, and is important for overall fecundity. We sequenced the Zfp36l3 gene from more than 20 representative species, from members of the Muridae, Cricetidae and Nesomyidae families. Zfp36l3 was not present in Dipodidae, or any families that branched earlier, indicating that this gene is exclusive to the Muroidea superfamily. We provide evidence that Zfp36l3 arose by retrotransposition of an mRNA encoded by a related gene, Zfp36l2 into an ancestral rodent X chromosome. Zfp36l3 has evolved rapidly since its origin, and numerous modifications have developed, including variations in start codon utilization, de novo intron formation by mechanisms including a nested retrotransposition, and the insertion of distinct repetitive regions. One of these repeat regions, a long alanine rich-sequence, is responsible for the full-time cytoplasmic localization of Mus musculus ZFP36L3. In contrast, this repeat sequence is lacking in Peromyscus maniculatus ZFP36L3, and this protein contains a novel nuclear export sequence that controls shuttling between the nucleus and cytosol. Zfp36l3 is an example of a recently acquired, rapidly evolving gene, and its various orthologues illustrate several different mechanisms by which new genes emerge and evolve.

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Section: Discussioncontrasting

confidence: 57%

Emergence and evolution of Zfp36l3

Gingerich

Stumpo

Lai

et al. 2016

Molecular Phylogenetics and Evolution

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“…Remarkably, replacement of the TZF domain in S. pombe Zfs1 with the TZF domain from either human TTP or the eudicot plant, C. odorata , completely complemented the abnormal flocculation and gene expression phenotypes seen in the Zfs1-deficient yeast (Fig. 3) [24]. These data suggest that there has been strong positive evolutionary pressure to maintain the RNA binding capabilities of the TZF domain over vast periods of evolution.…”

Section: Phylogenetic Distribution Of the Ttp Protein Familymentioning

confidence: 99%

“…The y-axis represents normalized RNA counts for the arz1 transcript, shown as mean values from at least four independent isolates, +/- SD. Modified from [24], with permission.…”

Section: Figurementioning

confidence: 99%

An Ancient Family of RNA-Binding Proteins: Still Important!

Wells

Perera

Blackshear

2017

Trends in Biochemical Sciences

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RNA binding proteins can be important modulators of mRNA stability, a critical process that determines the ultimate cellular levels of mRNAs and their encoded proteins. The tristetraprolin or TTP family of RNA binding proteins appeared early in the evolution of eukaryotes, and has persisted in modern eukaryotes. The domain structures and biochemical functions of family members from widely divergent lineages are remarkably similar, but their mRNA “targets” can be quite different, even in closely related species. Recent gene knockout studies in species as distantly related as plants, flies, yeasts and mice have demonstrated crucial roles for these proteins in a wide variety of physiological processes. Inflammatory and hematopoietic phenotypes in mice have suggested potential therapeutic approaches for analogous human disorders.

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“…In this case, we examined a readily assayable external phenotype, the propensity of the KO cells to flocculate in the presence of calcium (Wells et al, ). We also evaluated the molecular phenotype of the cells, by comparing the increased expression of Zfs1 target transcripts in KO and zinc finger mutant cells (Cuthbertson, Liao, Birnbaumer, & Blackshear, ; Wells et al, ; Wells, Hicks, Perera, & Blackshear, ). As in the case of the mice, both the external, flocculation phenotype, and the molecular phenotype involving increased expression of Zfs1 targets, were essentially identical in the KO and zinc finger mutant cells (Wells, Hicks, et al, ).…”

Section: The Linker Regionmentioning

confidence: 99%

The tandem zinc finger RNA binding domain of members of the tristetraprolin protein family

et al. 2019

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Tristetraprolin (TTP), the prototype member of the protein family of the same name, was originally discovered as the product of a rapidly inducible gene in mouse cells. Development of a knockout (KO) mouse established that absence of the protein led to a severe inflammatory syndrome, due in part to elevated levels of tumor necrosis factor (TNF). TTP was found to bind directly and with high affinity to specific AU‐rich sequences in the 3′‐untranslated region of the TNF mRNA. This initial binding led to promotion of TNF mRNA decay and inhibition of its translation. Many additional TTP target mRNAs have since been identified, some of which are cytokines and chemokines involved in the inflammatory response. There are three other proteins in the mouse with similar activities and domain structures, but whose KO phenotypes are remarkably different. Moreover, proteins with similar domain structures and activities have been found throughout eukaryotes, demonstrating that this protein family arose from an ancient ancestor. The defining characteristic of this protein family is the tandem zinc finger (TZF) domain, a 64 amino acid sequence with many conserved residues that is responsible for the direct RNA binding. We discuss here many aspects of this protein domain that have been elucidated since the original discovery of TTP, including its sequence conservation throughout eukarya; its apparent continued evolution in some lineages; its functional dependence on many key conserved residues; its “interchangeability” among evolutionarily distant species; and the evidence that RNA binding is required for the physiological functions of the proteins. This article is categorized under: RNA Interactions with Proteins and Other Molecules > RNA‐Protein Complexes RNA Interactions with Proteins and Other Molecules > Protein–RNA Recognition RNA Interactions with Proteins and Other Molecules > Protein–RNA Interactions: Functional Implications

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Functional Equivalence of an Evolutionarily Conserved RNA Binding Module

Cited by 15 publications

References 26 publications

Emergence and evolution of Zfp36l3

Emergence and evolution of Zfp36l3

An Ancient Family of RNA-Binding Proteins: Still Important!

The tandem zinc finger RNA binding domain of members of the tristetraprolin protein family

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