Translational Regulation of the JunD Messenger RNA

Short, Johnny D; Pfarr, Curt M.

doi:10.1074/jbc.m204553200

Cited by 55 publications

(44 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, Hartman et al (2006) demonstrated that the PCE-like element in the 59 UTR of human JunD mRNA interacts with RHA and regulates translation. JunD protein regulates cell growth in response to a stress, so tightly controlled translational regulation provides the means to rapidly alter protein expression (van Dam and Castellazzi 2001;Short and Pfarr 2002). During cap-dependant translation initiation, RHA ensures unwinding of the secondary structures in the 59 UTR to facilitate ribosomal scanning (Kozak 1989;Sonenberg and Gingras 1998;Merrick 2004).…”

Section: Introductionmentioning

confidence: 99%

A novel role of RNA helicase A in regulation of translation of type I collagen mRNAs

Manojlovic

Stefanovic²

2011

RNA

View full text Add to dashboard Cite

Type I collagen is composed of two a1(I) polypeptides and one a2(I) polypeptide and is the most abundant protein in the human body. Expression of type I collagen is primarily controlled at the level of mRNA stability and translation. Coordinated translation of a(I) and a2(I) mRNAs is necessary for efficient folding of the corresponding peptides into the collagen heterotrimer. In the 59 untranslated region (59 UTR), collagen mRNAs have a unique 59 stem-loop structure (59 SL). La ribonucleoprotein domain family member 6 (LARP6) is the protein that binds 59 SL with high affinity and specificity and coordinates their translation. Here we show that RNA helicase A (RHA) is tethered to the 59 SL of collagen mRNAs by interaction with the C-terminal domain of LARP6. In vivo, collagen mRNAs immunoprecipitate with RHA in an LARP6-dependent manner. Knockdown of RHA prevents formation of polysomes on collagen mRNAs and dramatically reduces synthesis of collagen protein, without affecting the level of the mRNAs. A reporter mRNA with collagen 59 SL is translated three times more efficiently in the presence of RHA than the same reporter without the 59 SL, indicating that the 59 SL is the cis-acting element conferring the regulation. During activation of quiescent cells into collagen-producing cells, expression of RHA is highly up-regulated. We postulate that RHA is recruited to the 59 UTR of collagen mRNAs by LARP6 to facilitate their translation. Thus, RHA has been discovered as a critical factor for synthesis of the most abundant protein in the human body.

show abstract

Section: Introductionmentioning

confidence: 99%

A novel role of RNA helicase A in regulation of translation of type I collagen mRNAs

Manojlovic

Stefanovic²

2011

RNA

View full text Add to dashboard Cite

show abstract

“…The longer and structured 5 0 UTR and alternative initiation codons in junD are features discordant with efficient cap-dependent translation initiation. Short and Pfarr (2002) investigated the possibility that the complex features of the junD 5 0 UTR promote internal initiation by ribosome recruitment to an internal ribosome entry site. Cap-independent internal ribosome entry is utilized by some viruses and cellular RNAs that exhibit a long and structured 5 0 UTR (reviewed by Baird et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

“…Intron removal has been shown to facilitate mRNA translation in the cytoplasm and presently is attributed to the activity of a multi-component exon junction complex that is deposited near exon-exon junctions (Braddock et al, 1994;Matsumoto et al, 1998;Wiegand et al, 2003;Nott et al, 2004;Tange et al, 2004;Gudikote et al, 2005). Second, the junD gene encodes a G/C-rich (86%) and relatively long 5 0 untranslated region (UTR; Figure 1; Short and Pfarr, 2002). Third, initiation of translation at alternative AUG codons results in two biochemically distinct Figure 1 The regulation of JunD activity is operated by interrelated layers of transcriptional, post-transcriptional and posttranslational control.…”

Section: Introductionmentioning

confidence: 99%

“…ERK, extracellular signal-regulated kinase; HDAC, histone deacetylase; JNK, Jun N-terminal kinase; MEN1, multiple endocrine neoplasia type-1; PCE, posttranscriptional control element; RHA, RNA helicase A; TPA, 12-O-tetradecanoyl-phorbol-13-acetate; TRE, TPA-response element. isoforms of JunD that orchestrate different proteinprotein interactions (Okazaki et al, 1998;Short and Pfarr, 2002). The two isoforms of JunD are a full-length, 39-kDa protein, and a 34-kDa protein that lacks 43 amino acids at the N-terminus (DJunD in Figure 1; Short and Pfarr, 2002).…”

Section: Introductionmentioning

confidence: 99%

“…isoforms of JunD that orchestrate different proteinprotein interactions (Okazaki et al, 1998;Short and Pfarr, 2002). The two isoforms of JunD are a full-length, 39-kDa protein, and a 34-kDa protein that lacks 43 amino acids at the N-terminus (DJunD in Figure 1; Short and Pfarr, 2002). Efficient cap-dependent translation initiation is favored by relatively short (less than 100 nt) and unstructured 5 0 UTR and by single AUG translation initiation codon embedded in a robust consensus Kozak sequence (5 0 -GCC(A/G)CCAUGG-3 0 ) (Kozak, 1984a(Kozak, , 1984bMerrick and Hershey, 1996;Yilmaz et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Multiple facets of junD gene expression are atypical among AP-1 family members

et al. 2008

View full text Add to dashboard Cite

JunD is a versatile AP-1 transcription factor that can activate or repress a diverse collection of target genes. Precise control of junD expression and JunD proteinprotein interactions modulate tumor angiogenesis, cellular differentiation, proliferation and apoptosis. Molecular and clinical knowledge of two decades has revealed that precise JunD activity is elaborated by interrelated layers of constitutive transcriptional control, complex post-transcriptional regulation and a collection of post-translational modifications and protein-protein interactions. The stakes are high, as inappropriate JunD activity contributes to neoplastic, metabolic and viral diseases. This article deconvolutes multiple layers of control that safeguard junD gene expression and functional activity. The activity of JunD in transcriptional activation and repression is integrated into a regulatory network by which JunD exerts a pivotal role in cellular growth control. Our discussion of the JunD regulatory network integrates important open issues and posits new therapeutic targets for the neoplastic, metabolic and viral diseases associated with JunD/AP-1 expression.

show abstract