Subcellular mRNA localisation at a glance

Parton, Richard M.; Davidson, Alexander; Davis, Ilan; Weil, Timothy T

doi:10.1242/jcs.114272

Cited by 30 publications

(35 citation statements)

References 111 publications

(109 reference statements)

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“…These new features of StAR transcription also provide a novel perspective on the relationship between transcription and splicing (Parton et al, 2014). First, the PKA stimulation of transcriptional elongation stalls near the translation termination site in exon 7, without initiation of splicing or reaching the alternative polyadenylation sites (Duan and Jefcoate, 2007; Duan et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

Stimulation of StAR expression by cAMP is controlled by inhibition of highly inducible SIK1 via CRTC2, a co-activator of CREB

Lee

Tong

Takemori

et al. 2015

Molecular and Cellular Endocrinology

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In mouse steroidogenic cells the activation of cholesterol metabolism is mediated by steroidogenic acute regulatory protein (StAR). Here, we visualized a coordinated regulation of StAR transcription, splicing and post-transcriptional processing, which are synchronized by salt inducible kinase (SIK1) and CREB-regulated transcription coactivator (CRTC2). To detect primary RNA (pRNA), spliced primary RNA (Sp-RNA) and mRNA in single cells, we generated probe sets by using fluorescence in situ hybridization (FISH). These methods allowed us to address the nature of StAR gene expression and to visualize protein–nucleic acid interactions through direct detection. We show that SIK1 represses StAR expression in Y1 adrenal and MA10 testis cells through inhibition of processing mediated by CRTC2. Digital image analysis matches qPCR analyses of the total cell culture. Evidence is presented for spatially separate accumulation of StAR pRNA and Sp-RNA at the gene loci in the nucleus. These findings establish that cAMP, SIK and CRTC mediate StAR expression through activation of individual StAR gene loci.

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Section: Discussionmentioning

confidence: 99%

Stimulation of StAR expression by cAMP is controlled by inhibition of highly inducible SIK1 via CRTC2, a co-activator of CREB

Lee

Tong

Takemori

et al. 2015

Molecular and Cellular Endocrinology

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“…For successful intracellular replication, the Pol-pgRNA complex is encapsidated. Also, it has been shown that RNAs themselves can localize to specific subcellular locations for local protein production (58). If the majority of Pol is at the mitochondria, we wanted to determine whether Cp and pgRNA also localize to the mitochondria.…”

Section: Studying Hbv Subcellular Localization During Infectionmentioning

confidence: 99%

Hepatitis B Virus Polymerase Localizes to the Mitochondria, and Its Terminal Protein Domain Contains the Mitochondrial Targeting Signal

Unchwaniwala

Sherer

Loeb

2016

J Virol

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To understand subcellular sites of hepatitis B virus (HBV) replication, we visualized core (Cp), polymerase (Pol), and pregenomic RNA (pgRNA) in infected cells. Interestingly, we found that the majority of Pol localized to the mitochondria in cells undergoing viral replication. The mitochondrial localization of Pol was independent of both the cell type and other viral components, indicating that Pol contains an intrinsic mitochondrial targeting signal (MTS). Neither Cp nor pgRNA localized to the mitochondria during active replication, suggesting a role other than DNA synthesis for Pol at the mitochondria. The Pol of duck hepatitis B virus (DHBV) also localized to the mitochondria. This result indicates that localization of Pol to mitochondria is likely a feature of all hepadnaviruses. To map the MTS within HBV Pol, we generated a series of Pol-green fluorescent protein (Pol-GFP) fusions and found that a stretch spanning amino acids (aa) 141 to 160 of Pol was sufficient to target GFP to the mitochondria. Surprisingly, deleting aa 141 to 160 in full-length Pol did not fully ablate Pol's mitochondrial localization, suggesting that additional sequences are involved in mitochondrial targeting. Only by deleting the N-terminal 160 amino acids in fulllength Pol was mitochondrial localization ablated. Crucial residues for pgRNA packaging are contained within aa 141 to 160, indicating a multifunctional role of this region of Pol in the viral life cycle. Our studies show an unexpected Pol trafficking behavior that is uncoupled from its role in viral DNA synthesis. IMPORTANCEChronic infection by HBV is a serious health concern. Existing therapies for chronically infected individuals are not curative, underscoring the need for a better understanding of the viral life cycle to develop better antiviral therapies. To date, the most thoroughly studied function of Pol is to package the pgRNA and reverse transcribe it to double-stranded DNA within capsids. This study provides evidence for mitochondrial localization of Pol and defines the MTS. Recent findings have implicated a nonreverse transcription role for Pol in evading host innate immune responses. Mitochondria play an important role in controlling cellular metabolism, apoptosis, and innate immunity. Pol may alter one or more of these host mitochondrial functions to gain a replicative advantage and persist in chronically infected individuals.

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“…89 Once eIF4E binds to the 7-methyl guanosine cap at the 5 0 end, translation can be initiated by the subsequent binding of eIF4G which, in conjunction with eIF3, leads to recruitment of the 43S ribosomal pre-initiation complex. 90 Unlocalized or repressed mRNAs often have eIF4E-binding proteins bound to eIF4E, thus blocking this initiation. This process is reviewed in detail.…”

Section: Superimposition Of Translational Regulatory Mechanismsmentioning

confidence: 99%

mRNA localization in theDrosophilagermline

Weil

2014

RNA Biology

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Subcellular mRNA localisation at a glance

Cited by 30 publications

References 111 publications

Stimulation of StAR expression by cAMP is controlled by inhibition of highly inducible SIK1 via CRTC2, a co-activator of CREB

Stimulation of StAR expression by cAMP is controlled by inhibition of highly inducible SIK1 via CRTC2, a co-activator of CREB

Hepatitis B Virus Polymerase Localizes to the Mitochondria, and Its Terminal Protein Domain Contains the Mitochondrial Targeting Signal

mRNA localization in theDrosophilagermline

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