The stem–loop binding protein stimulates histone translation at an early step in the initiation pathway

Gorgoni, Barbara; Andrews, Stuart; Schaller, André; Schümperli, Daniel; Gray, Nicola K.; Müller, Berndt

doi:10.1261/rna.7281305

Cited by 59 publications

(79 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…MS2 Tethering-The MSP vector, the firefly Luc-MS2, and the CSFV-firefly Luc-MS2 reporter cDNAs were supplied by Nicola Gray (55,56). cDNAs encoding MS2-Xp54 were described previously (30).…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

CPEB Interacts with an Ovary-specific eIF4E and 4E-T in Early Xenopus Oocytes

Minshall

Reiter

Weil

et al. 2007

Journal of Biological Chemistry

168

240

View full text Add to dashboard Cite

CPEB (cytoplasmic polyadenylation element-binding protein) is an important regulator of translation in oocytes and neurons. Although previous studies of CPEB in late Xenopus oocytes involve the eIF4E-binding protein maskin as the key factor for the repression of maternal mRNA, a second mechanism must exist, since maskin is absent earlier in oogenesis. Using co-immunoprecipitation and gel filtration assays, we show that CPEB specifically interacts, via protein/protein interactions, with the RNA helicase Xp54, the RNA-binding proteins P100(Pat1) and RAP55, the eIF4E-binding protein 4E-T, and an eIF4E protein. Remarkably, these CPEB complex proteins have been characterized, in one or more organism, as P-body, maternal, or neuronal granule components. We do not detect interactions with eIF4E1a, the canonical cap-binding factor, eIF4G, or eIF4A or with proteins expressed late in oogenesis, including maskin, PARN, and 4E-BP1. The eIF4E protein was identified as eIF4E1b, a close homolog of eIF4E1a, whose expression is restricted to oocytes and early embryos. Although eIF4E1b possesses all residues required for cap and eIF4G binding, it binds m 7 GTP weakly, and in pull-down assays, rather than binding eIF4G, it binds 4E-T, in a manner independent of the consensus eIF4E-binding site, YSKEELL. Wild type and Y-A mutant 4E-T (which binds eIF4E1b but not eIF4E1a), when tethered to a reporter mRNA, represses its translation in a cap-dependent manner, and injection of eIF4E1b antibody accelerates meiotic maturation. Altogether, our data suggest that CPEB, partnered with several highly conserved RNA-binding partners, inhibits protein synthesis in oocytes using a novel pairing of 4E-T and eIF4E1b.Selective protein synthesis in oocytes, eggs, and early embryos of many organisms drives several critical aspects of early development, including meiotic maturation and entry into mitosis, establishment of embryonic axes, and cell fate determination. Protein synthesis is usually regulated at the initiation stage, mediated by the 5Ј m 7 GpppN mRNA cap structure bound by the translation initiation complex eIF4F, composed of eIF4E, the cap-binding protein, the RNA helicase eIF4A, and the large scaffold protein eIF4G, which has a consensus binding site YXXXXL for eIF4E, and additional sites for eIF3 and the poly(A)-binding protein. eIF3 recruits the small ribosomal subunit, whereas the eIF4E-eIF4G-poly(A)-binding protein relay results in the so-called "closed loop" model, responsible for the synergistic enhancement of translation by capped and polyadenylated mRNAs. A hallmark of translational control mechanisms is the role of mRNA-binding proteins, which recognize specific (and usually) 3Ј-UTR 2 cis-elements and influence the recruitment of the small ribosomal subunit to the 5Ј cap (reviewed in Refs. 1-3). Probably, the best studied mRNA-binding protein is CPEB1 (cytoplasmic polyadenylation-binding protein 1), characterized in flies, worms, clams, Aplysia, Xenopus, and mammals, which in its conserved C terminus contains two tandem RNA reco...

show abstract

Section: Methodsmentioning

confidence: 99%

“…To assess the dependence of the repression mechanism on the 5Ј cap structure, we first compared the level of translation of (nonadenylated) Fluc RNAs bearing m 7 GpppG or ApppG caps or the CSFV IRES (56). The IRES reporter RNA was capped with ApppG to avoid degradation.…”

Section: Xeif4e1b Is Cytoplasmic and Its Expression Is Limited To Oocmentioning

confidence: 99%

CPEB Interacts with an Ovary-specific eIF4E and 4E-T in Early Xenopus Oocytes

Minshall

Reiter

Weil

et al. 2007

Journal of Biological Chemistry

168

240

View full text Add to dashboard Cite

show abstract

“…By contrast, 2Apro does not alter translational stimulation by tethered stem-loopbinding protein (SLBP) (Fig. 4C), a translational activator that acts independently of the PABP-eIF4G interaction (23,24). This result establishes eIF4G as the PABP partner required to mediate the cap-independent effects of ICP27 on translation initiation.…”

Section: Icp27 Stimulates Initiation Of Translation Independently Of Thementioning

confidence: 97%

Viral and cellular mRNA-specific activators harness PABP and eIF4G to promote translation initiation downstream of cap binding

Smith

Anderson

Larralde

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

Regulation of mRNA translation is a major control point for gene expression and is critical for life. Of central importance is the complex between cap-bound eukaryotic initiation factor 4E (eIF4E), eIF4G, and poly(A) tail-binding protein (PABP) that circularizes mRNAs, promoting translation and stability. This complex is often targeted to regulate overall translation rates, and also by mRNA-specific translational repressors. However, the mechanisms of mRNA-specific translational activation by RNA-binding proteins remain poorly understood. Here, we address this deficit, focusing on a herpes simplex virus-1 protein, ICP27. We reveal a direct interaction with PABP that is sufficient to promote PABP recruitment and necessary for ICP27-mediated activation. PABP binds several translation factors but is primarily considered to activate translation initiation as part of the PABP-eIF4G-eIF4E complex that stimulates the initial cap-binding step. Importantly, we find that ICP27-PABP forms a complex with, and requires the activity of, eIF4G. Surprisingly, ICP27-PABP-eIF4G complexes act independently of the effects of PABP-eIF4G on cap binding to promote small ribosomal subunit recruitment. Moreover, we find that a cellular mRNA-specific regulator, Deleted in Azoospermia-like (Dazl), also employs the PABP-eIF4G interaction in a similar manner. We propose a mechanism whereby diverse RNA-binding proteins directly recruit PABP, in a non-poly(A) tail-dependent manner, to stimulate the small subunit recruitment step. This strategy may be particularly relevant to biological conditions associated with hypoadenylated mRNAs (e.g., germ cells/neurons) and/or limiting cytoplasmic PABP (e.g., viral infection, cell stress). This mechanism adds significant insight into our knowledge of mRNA-specific translational activation and the function of the PABP-eIF4G complex in translation initiation.D espite the importance of translational control, the mechanisms by which specific subsets of mRNAs are translationally regulated are only well defined in a handful of cases. Nevertheless, it is clear that regulation is most often mediated by factors recruited to the 3′ untranslated region (UTR) of mRNAs and frequently occurs at the level of initiation (1). Initiation is a multistep process involving several mRNA-dependent steps, each of which requires eukaryotic initiation factors (eIFs) (2). Initially, the m 7 GpppX cap is bound by eIF4F, comprising a large scaffold protein, eIF4G, bound to the cap-binding protein, eIF4E, and an RNA helicase, eIF4A. The small (40S) ribosomal subunit, initiator tRNA, and associated initiation factors are then recruited as a 43S preinitiation complex. Recruitment is facilitated by eIF4A-dependent removal of RNA secondary structure and by the interaction of 40S-associated eIF3 with eIF4G. The 43S small ribosomal subunit complex then scans the 5′ UTR to locate a start codon, recognition of which promotes release of initiation factors and joining of the large (60S) ribosomal subunit to form an 80S ribosome. Like the cap,...

show abstract

“…Under in vivo conditions, SLBP is likely to be an essential factor in processing of all histone pre-mRNAs regardless of the HDE sequence and the extent of base pairing to the U7 snRNA (Pandey et al, 1994). Following processing, SLBP remains associated with the stem-loop at the 3' end and accompanies the mature histone mRNA to the cytoplasm (Dominski et al, 1995;Erkmann et al, 2005;Whitfield et al, 2004), where it stimulates its translation into histone proteins (Gorgoni et al, 2005;Sanchez and Marzluff, 2002).…”

Section: Stem-loop Binding Protein (Slbp)mentioning

confidence: 99%

“…During 3' end processing the HDE interacts with the U7 snRNP and the stem-loop is recognized by a protein termed the stem-loop binding protein (SLBP) . After completion of processing, SLBP remains associated with the stem-loop at the end of mature histone mRNAs and stimulates their translation into histone proteins in the cytoplasm (Gorgoni et al, 2005;Sanchez and Marzluff, 2002). The intracellular concentration of SLBP reaches the highest level during S phase and rapidly declines during the S/G2 transition due to proteasome degradation (Whitfield et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

Formation of the 3′ end of histone mRNA: Getting closer to the end

Domiński

Marzluff

2007

Gene

155

180

View full text Add to dashboard Cite

Nearly all eukaryotic mRNAs end with a poly (A) tail that is added to their 3' end by the ubiquitous cleavage/polyadenylation machinery. The only known exception to this rule are metazoan replication dependent histone mRNAs, which end with a highly conserved stem-loop structure. This distinct 3' end is generated by specialized 3'end processing machinery that cleaves histone pre-mRNAs 4-5 nucleotides downstream of the stem-loop and consists of the U7 small nuclear RNP (snRNP) and number of protein factors. Recently, the U7 snRNP has been shown to contain a unique Sm core that differs from that of the spliceosomal snRNPs, and an essential heat labile processing factor has been identified as symplekin. In addition, cross-linking studies have pinpointed CPSF-73 as the endonuclease, which catalyzes the cleavage reaction. Thus, many of the critical components of the 3' end processing machinery are now identified. Strikingly, this machinery is not as unique as initially thought but contains a number of factors involved in cleavage/polyadenylation, suggesting that the two mechanisms have a common evolutionary origin. The greatest challenge that lies ahead is to determine how all these factors interact with each other to form a catalytically competent processing complex capable of cleaving histone pre-mRNAs.

show abstract

The stem–loop binding protein stimulates histone translation at an early step in the initiation pathway

Cited by 59 publications

References 43 publications

CPEB Interacts with an Ovary-specific eIF4E and 4E-T in Early Xenopus Oocytes

CPEB Interacts with an Ovary-specific eIF4E and 4E-T in Early Xenopus Oocytes

Viral and cellular mRNA-specific activators harness PABP and eIF4G to promote translation initiation downstream of cap binding

Formation of the 3′ end of histone mRNA: Getting closer to the end

Contact Info

Product

Resources

About