Autoregulation of poly(A)-binding protein synthesis<i>in vitro</i>

Neto, Osvaldo P. de Melo; Standart, Nancy; de, Cezar Martins

doi:10.1093/nar/23.12.2198

Cited by 108 publications

(107 citation statements)

References 55 publications

(47 reference statements)

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“…The RNA was transcribed from a construct lacking the normal RB47 5Ј UTR, as the expressed precursor protein binds to its own 5Ј UTR, interfering with in vitro translation and chloroplast import (data not shown). Binding of other PABPs to their own 5Ј UTRs has been shown to block in vitro translation, and has therefore been implicated in regulation of protein expression in vivo (39,40). As shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

A poly(A) binding protein functions in the chloroplast as a message-specific translation factor

Yohn

Cohen

Danon

et al. 1998

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

105

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High-affinity binding of a set of proteins with specificity for the 5 untranslated region (UTR) of the Chlamydomonas reinhardtii chloroplast psbA mRNA correlates with light-regulated translational activation of this message. We have isolated a cDNA encoding the main psbA RNA binding protein, RB47, and identified this protein as a member of the poly(A) binding protein family. Poly(A) binding proteins are a family of eukaryotic, cytoplasmic proteins thought to bind poly(A) tails of mRNAs and play a role in translational regulation. In vitro translation of RNA transcribed from the RB47 cDNA produces a precursor protein that is efficiently transported into the chloroplast and processed to the mature 47-kDa protein. RB47 expressed and purified from Escherichia coli binds to the psbA 5 UTR with similar specificity and affinity as RB47 isolated from C. reinhardtii chloroplasts. The identification of a normally cytoplasmic translation factor in the chloroplast suggests that the prokaryotic-like chloroplast translation machinery utilizes a eukaryotic-like initiation factor to regulate the translation of a key chloroplast mRNA. These data also suggest that poly(A) binding proteins may play a wider role in translation regulation than previously appreciated.

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Section: Resultsmentioning

confidence: 99%

A poly(A) binding protein functions in the chloroplast as a message-specific translation factor

Yohn

Cohen

Danon

et al. 1998

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

105

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“…The data in this report show that there are at least two different mechanisms by which translation initiation can be regulated by 5Ј UTR mRNA binding proteins: inhibition of 43S complex recruitment (as in IRE.34 mRNA) and stalled scanning without inhibited 43S complex recruitment (as in IRE.100 mRNA). The newly identified mechanism of stalled scanning by cap-distal RNA-protein complexes could potentially explain known examples of translational control, such as the autoregulation of poly(A)-binding protein mRNA by poly(A)-binding protein (5) or the regulation of Drosophila msl-2 mRNA by the Sex-lethal protein (3,8,21). The regulation of F64 and IRE.66 mRNAs may result from a composite of the two mechanisms described above.…”

Section: Discussionmentioning

confidence: 99%

Ribosomal Pausing and Scanning Arrest as Mechanisms of Translational Regulation from Cap-Distal Iron-Responsive Elements

Paraskeva

Gray

Schläger

et al. 1999

Molecular and Cellular Biology

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Iron regulatory protein 1 (IRP-1) binding to an iron-responsive element (IRE) located close to the cap structure of mRNAs represses translation by precluding the recruitment of the small ribosomal subunit to these mRNAs. This mechanism is position dependent; reporter mRNAs bearing IREs located further downstream exhibit diminished translational control in transfected mammalian cells. To investigate the underlying mechanism, we have recapitulated this position effect in a rabbit reticulocyte cell-free translation system. We show that the recruitment of the 43S preinitiation complex to the mRNA is unaffected when IRP-1 is bound to a cap-distal IRE. Following 43S complex recruitment, the translation initiation apparatus appears to stall, before linearly progressing to the initiation codon. The slow passive dissociation rate of IRP-1 from the cap-distal IRE suggests that the mammalian translation apparatus plays an active role in overcoming the cap-distal IRE-IRP-1 complex. In contrast, cap-distal IRE-IRP-1 complexes efficiently repress translation in wheat germ and yeast translation extracts. Since inhibition occurs subsequent to 43S complex recruitment, an efficient arrest of productive scanning may represent a second mechanism by which RNA-protein interactions within the 5 untranslated region of an mRNA can regulate translation. In contrast to initiating ribosomes, elongating ribosomes from mammal, plant, and yeast cells are unaffected by IRE-IRP-1 complexes positioned within the open reading frame. These data shed light on a characteristic aspect of the IRE-IRP regulatory system and uncover properties of the initiation and elongation translation apparatus of eukaryotic cells.The regulation of iron metabolism by the iron-responsive element (IRE)-iron regulatory protein (IRP) system represents an intensively studied example of translational control in higher eukaryotes. Several mRNAs encoding proteins involved in cellular iron metabolism harbor an IRE at a cap-proximal position of their 5Ј untranslated regions (UTRs). The IRE is specifically recognized by IRP-1 and IRP-2, which bind to and repress the translation of IRE-containing mRNAs both in vivo and in vitro (17,39). Translational control by specific mRNAprotein interactions is commonly enacted at the level of translation initiation (e.g., caudal [6, 38], 15-lipoxygenase [35, 36], and oskar [22,43]). IRP binding to the IRE of ferritin mRNAs affects an early step of translation initiation: it prevents the recruitment of the 43S translation preinitiation complex (which includes the small ribosomal subunit) (13, 33). Transfection studies using mammalian tissue culture cells revealed a characteristic feature of this IRE-IRP regulatory mechanism: for IRP binding to efficiently block translation, the IRE must be located within Ͻ60 nucleotides from the m 7 GpppN-cap structure of the mRNA (9, 10). An IRE placed Ͼ60 nucleotides downstream from the cap structure mediates only partial translational inhibition by IRP binding. In keeping with this position effect, the cap-...

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“…As with the IRE/IRP interaction, binding may be regulated by a redox mechanism involving protein -SH groups [265]. The poly(A)-binding protein (PABP) represses its own translation by binding to an oligo(A) sequence found in the 5' UTR of all PABP mRNAs so far examined [266]. This repression can be relieved in vitro by addition of exogenous poly(A), which competes the binding protein off the 5' UTR.…”

Section: Structural Features In the Untranslated Regions Of Mrnas Thamentioning

confidence: 99%

Initiation of Protein Synthesis in Eukaryotic Cells

Pain

1996

European Journal of Biochemistry

673

470

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It is becoming increasingly apparent that translational control plays an important role in the regulation of gene expression in eukaryotic cells. Most of the known physiological effects on translation are exerted at the level of polypeptide chain initiation. Research on initiation of translation over the past five years has yielded much new information, which can be divided into three main areas: (a) structure and function of initiation factors (including identification by sequencing studies of consensus domains and motifs) and investigation of protein-protein and protein-RNA interactions during initiation ; (b) physiological regulation of initiation factor activities and (c) identification of features in the 5' and 3' untranslated regions of messenger RNA molecules that regulate the selection of these mRNAs for translation. This review aims to assess recent progress in these three areas and to explore their interrelationships.Keywords: translation; initiation; mRNA ; review, regulation.In 1986 I published a review describing the mechanism and regulation of initiation of translation in mammalian cells 121. By that time most of the polypeptide initiation factors catalysing this process had been extensively purified and their individual activities studied in various in vitro systems. Several of them had been shown to be phosphoproteins and, in one case, eukaryotic initiation factor-2 (eIF-2), the effects of phosphorylation had been elucidated and two physiological kinases had been identified. There seemed to be a feeling in some circles that the most interesting problems in protein synthesis had been solved, and that only a few rather boring nuts and bolts awaited discovery.Over the intervening ten years there has been an explosion of research activity in this area, largely fuelled by information yielded by molecular biology and genetic techniques. Cloning of cDNAs encoding initiation factors has revealed domain structures indicative of function and potential regulatory mechanisms. Experiments exploiting the ability to elucidate and manipulate mRNA sequences have demonstrated that translational control contributes to changes in patterns of gene expression during growth, differentiation and development to an extent that would have seemed inconceivable in 1985. Such experiments have, in particular, revealed important roles for structural fea- UTR, untranslated region (in mRNA); RRM, RNA recognition motif; ORF, open reading frame; EMCV, encephalomyocarditis virus ; FMDV, foot-and-mouth disease virus ; IRES, internal ribosome entry segment ; PTB, polypyrimidine tract binding protein ; HCR, heme-controlled repressor; PKR, protein kinase activated by RNA; dsRNA, doublestranded RNA; p70ShK and p 9 0 k , 70 kDa and 90-92 kDa ribosomal protein S6 kinases ; GSK, glycogen synthase kinase ; IRE, iron-regulatory element; IRP, iron regulatory protein ; PABP, poly(A) binding protein; AMV, alfalfa mosaic virus ; CPE, cytoplasmic polyadenylation element (also known as ACE, adenylation control element); MAP, mitogenactivated protei...

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Autoregulation of poly(A)-binding protein synthesisin vitro

Abstract: The poly(A)-blnding pin (PABP), in a complx with the 3' poly(A) tall of eUkaryotic mRNAs, plays important roles in the contol of translation and message stability. All

Cited by 108 publications

References 55 publications

A poly(A) binding protein functions in the chloroplast as a message-specific translation factor

A poly(A) binding protein functions in the chloroplast as a message-specific translation factor

Ribosomal Pausing and Scanning Arrest as Mechanisms of Translational Regulation from Cap-Distal Iron-Responsive Elements

Initiation of Protein Synthesis in Eukaryotic Cells

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