Messenger-RNA-binding proteins and the messages they carry

Dreyfuss, Gideon; Kim, V. Narry; Kataoka, Naoyuki

doi:10.1038/nrm760

Cited by 1,287 publications

(1,140 citation statements)

References 160 publications

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“…Indeed, many cellular IRESs are almost completely inactive when present in dicistronic mRNAs introduced directly into the cytoplasm (by RNA transfection), suggesting that a 'nuclear experience' is an essential prerequisite for internal initiation. 63 Certain ITAFs, including PTB, PCBP1, unr and hnRNPK, are known to able to shuttle between the nucleus and the cytoplasm [64][65][66] and it is therefore possible that complexes between IRESs and ITAFs are formed in the nucleus. Cell signalling pathways that are activated in apoptosis are probably involved in the regulation of IRES-mediated protein synthesis via modulation of the activity or localization of the trans-acting factors.…”

Section: Regulation Of Itafs During Apoptosismentioning

confidence: 99%

Internal ribosome entry segment-mediated translation during apoptosis: the role of IRES-trans-acting factors

et al. 2005

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During apoptosis, there is a reduction in translation initiation caused by caspase cleavage of several of the factors required for the cap-dependent scanning mechanism. Under these circumstances, many proteins that are required for apoptosis are instead translated by the alternative method of internal ribosome entry. This mechanism requires the formation of a complex RNA structural element and in the presence of internal ribosome entry segment (IRES)-trans-acting factors (ITAFs), the ribosome is recruited to the RNA. The interactions of several ITAFs with IRESs have been investigated in detail, and several mechanisms of action have been noted, including acting as chaperones, stabilising and remodelling the RNA structure. Structural remodelling by PTB in particular will be discussed, and how this protein is able to facilitate recruitment of the ribosome to several IRESs by causing previously occluded sites to become more accessible.

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Section: Regulation Of Itafs During Apoptosismentioning

confidence: 99%

Internal ribosome entry segment-mediated translation during apoptosis: the role of IRES-trans-acting factors

et al. 2005

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“…Mammalian splicing regulators mostly belong to two superfamilies, the SR/SR-like and hnRNP proteins, neither of which is exclusively involved in alternative splicing (Dreyfuss et al, 2002;Graveley, 2000). The former are also components of the spliceosome, whereas the latter are also involved in pre-mRNA transport, RNA stability and translational regulation.…”

Section: Introductionmentioning

confidence: 99%

SR protein 9G8 modulates splicing of tau exon 10 via its proximal downstream intron, a clustering region for frontotemporal dementia mutations

Gao

Wang

et al. 2007

Molecular and Cellular Neuroscience

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The microtubule-associated protein tau is important to normal neuronal function in the mammalian nervous system. Aggregated tau is the major component of neurofibrillary tangles (NFTs), present in several neurodegenerative diseases, including Alzheimer's and frontotemporal dementia with Parkinsonism (FTDP). Splicing misregulation of adult-specific exon 10 results in expression of abnormal ratios of tau isoforms, leading to FTDP. Positions +3 to +16 of the intron downstream of exon 10 define a clustering region for point mutations that are found in FTDP. The serine/argininerich (SR) factor 9G8 strongly inhibits inclusion of tau exon 10. In this study, we established that 9G8 binds directly to this clustering region, requires a wild-type residue at position +14 to inhibit exon inclusion, and RNAi constructs against 9G8 increase exon 10 inclusion. These results indicate that 9G8 plays a key role in regulation of exon 10 splicing and imply a pathogenic role in neurodegenerative diseases.

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“…The mRNA processing, as well as other mRNArelated cell activities, are regulated by specific RNA-binding proteins such as the members of the hnRNP family [8]. About 20 major hnRNP proteins, from A1 to U, have been described and included in the family by their capacity to bind to pre-mRNA with no unique structural motif or function.…”

Section: Introductionmentioning

confidence: 99%

“…Rather, specific combinations of hnRNP proteins are thought to cluster on each type of pre-mRNA. This particular combination would depend on the mRNA sequence and the repertoire of hnRNP proteins present in the nucleus at the moment of transcription [8]. hnRNP proteins are involved in a variety of key cellular functions such as mRNA splicing [12], stabilization [13,14], nucleo-cytoplasmic transport [15 Á/17], and transcriptional control [18].…”

Section: Introductionmentioning

confidence: 99%

Altered patterns of expression of members of the heterogeneous nuclear ribonucleoprotein (hnRNP) family in lung cancer

et al. 2003

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Summary hnRNP A2/B1 has been suggested as a useful early detection marker for lung carcinoma. hnRNP A2/B1 is a member of a large family of heterogeneous nuclear ribonucleoproteins (hnRNP proteins) involved in a variety of functions, including regulation of transcription, mRNA metabolism, and translation. In lung cancer, we have evaluated the expression and cellular localization of several members of the hnRNP family, hnRNP A1, A2, B1, C1, C2 and K. 16 cell lines (SCLC and NSCLC) and biopsies from 32 lung cancer patients were analyzed. Our results suggest that, besides hnRNP A2/B1, the expression of other members of the hnRNP family is altered both in SCLC and NSCLC. In the biopsies, negative or low expression of the hnRNP proteins analyzed was observed in normal epithelial cells whereas lung cancer cells showed highly intense nuclear or cytoplasmic immunolocalization. In all the lung cancer cell lines, the mRNA for all the hnRNP proteins was detected. In general, higher levels of hnRNP mRNAs were found in SCLC as compared with NSCLC. Our results also suggest that the expression and processing of each hnRNP protein in lung cancer is independently regulated and is not exclusively related to proliferation status. In SCLC cell lines, hnRNP A1 protein expression correlated with that of Bcl-x L . In the lung cancer cell lines, hnRNP K protein localization varied with the cellular confluence.

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Messenger-RNA-binding proteins and the messages they carry

Cited by 1,287 publications

References 160 publications

Internal ribosome entry segment-mediated translation during apoptosis: the role of IRES-trans-acting factors

Internal ribosome entry segment-mediated translation during apoptosis: the role of IRES-trans-acting factors

SR protein 9G8 modulates splicing of tau exon 10 via its proximal downstream intron, a clustering region for frontotemporal dementia mutations

Altered patterns of expression of members of the heterogeneous nuclear ribonucleoprotein (hnRNP) family in lung cancer

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