HnRNPs

MK2 (also termed MAP kinase-activated protein kinase 2, MAPKAP-K2) is activated by p38 MAP kinase a// (Kotlyarov et al, 2002 Roux and Blenis, 2004). MK2 plays a key role in the control of the production of certain cytokines, for example, tumor necrosis factor a. MK2 does so by phosphorylating proteins that bind specifically to the regulatory regions in the S untranslated regions (UTRs) of such mRNAs (Hitti et al, 2006). These regions contain AU-rich elements (AREs) to which proteins such as HnRNP A1 also bind. 

M9 domain Found in hnRNP Al Gly-rich 38 aa stretch also works as export signal Transportin/none... 

KNS Residues 323-361 of hnRNP K also works as export signal Unknown/unknown... 

Perrotti, D., V. Cesi, R. Trotta, C. Guerzoni, G. Santilli, K. Campbell, A. Ier-volino, F. Condorelli, C. Gambacorti-Passerini, M. A. Caligiuri, and B. Calabretta. 2002. BCR-ABL suppresses C/EBPalpha expression through inhibitory action of hnRNP E2. Nat Genet 30(l) 48-58. 

Nucleolin together with HnRNP D has been shown to form the LRl transcription factor. LRl is a B cell-specific, sequence-specific DNA binding activity that regulates transcription in activated B cells (Hanakahi et at, 1997 Hanakahi and Maizels, 2000). DNA bending induced by nucleolin and hnRNP D might regulate the transcriptional activation by LRl (Hanakahi and Maizels, 2000). 

Dempsey LA, Hanakahi LA, Maizels N (1998) A specific isoform of hnRNP D interacts with DNA in the LRl heterodimer canonical RNA binding motifs in a sequence-specific duplex DNA binding protein. J Biol Chem 273 29224-29229... 

Gohring F, Fackelmayer FO (1997) The scaffold/matrix attachment region binding protein hnRNP-U (SAF-A) is directly bound to chromosomal DNA in vivo a chemical cross-linking study. Biochemistry 36(27) 8276-8283... 

The composition of the spliceosome determines the pattern of chosen sphce sites. Several proteins have been identified which act as antagoiusts in the selection of sphce sites. The SF2 protein (and related proteins) belong to the family of SR proteins (SR Ser- and Arg-rich) and supports the use of 5 -sphce sites. Another protein, the hnRNP A1 protein supports the use of 3 -splice sites. 

Burd, C.G. and Dreyfuss, G. (1994) RNA binding specificity of hnRNP Al significance of hnRNP A1 high-affinity binding sites in pre-mRNA splicing. EMBOJ., 13, 1197-1204. 

Izaurralde, E., Jarmolowski, A., Beisel, C., Mattaj, I.W., Dreyfuss, G. and Fischer, U. (1997a) A role for the M9 transport signal of hnRNP Al in mRNA nuclear export. J. Cell Biol, 137,27-35. 

In addition to RNA-binding domains, the auxiliary domains are important components of the hnRNPs (Biamonti and Riva, 1994). Unlike RNA-binding domains, these domains are unstructured and have diverse sequences, making their classification difficult. The best characterized domain is the glycine-rich type found in hnRNPs Al and A2/B1. In hnRNP Al, the glycine-rich domain is localized near the C-terminus and is... 

Figure 13.1 Schematic representation of mRNA biogenesis. The nascent mRNA associates with a subset of RNA-binding proteins, termed heterogeneous nuclear ribonucleoproteins (hnRNPs) and splicing. Through specific protein-protein, hnRNPs direct the assembly of processing factors to the newly synthesized mRNA. hnRNPs remain associated with the pre-mRNA until processing is complete and some stay with the mature mRNA during nuclear export.

The shuttling of some hnRNPs and their presence in the cytoplasm suggests that they play a role in the cytoplasmic metabolism of mRNA. It appears that the nuclear history of mRNAs influences their cytoplasmic fate, providing the cell with a new level for the control of gene expression (Matsumoto et al., 1998). The possibility exists that the shuttling hnRNPs are important players in this process. 

Cartegni, L., Maconi, M., Morandi, E., Cobianchi, F., Riva, S. and Biamonti, G. (1996) hnRNP A 1 selectively interacts through its Gly-rich domain with different RNA-binding proteins. J. Mol. Biol, 259, 337-348. 

Dreyfuss, G., Matunis, M.J., Pinol-Roma, S. and Burd, C.G. (1993) hnRNP proteins and the biogenesis of mRNA. Annu. Rev. Biochem., 62,289-321. 

Krecic, A M. and Swanson, M.S. (1999) hnRNP complexes composition, structure, and function. Curr. Opin. Cell Biol, 11, 363-371. 

Michael, W.M., Eder, P.S. and Dreyfuss, G. (1997) The K nuclear shuttling domain a novel signal for nuclear import and nuclear export in the hnRNP K protein. EMBO J., 16, 3587-3598. 

Stutz, F., Bachi, A., Doerks, T., Braun, I.C., Seraphin, B., Wilm, M. et al. (2000) REF, an evolutionary conserved family of hnRNP-like proteins, interacts with TAP/Mex67p and participates in mRNA nuclear export. RNA, 6, 638-650. 

Weighardt, F., Biamonti, F. and Riva, S. (1996) The roles of heterogeneous nuclear ribonucleoproteins (hnRNP) in RNA metabolism. BioEssay, 18, 747-756. 

Elammerhead ribozyme, 58, 61 Pleat shock protein (HSP), 18 Elepatic clearance, 414,418 Elepatic delivery, 455 Elistidine-rich peptides, 340 Elistidylated polylysines, 341 HIV-1 gp41, 356 hnRNPs, 262... 

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