Cap-Binding Proteins

 Most of the functions in the nucleus and cytoplasm of the cap of messenger RNA (mRNA) are mediated by cap-binding proteins (CBP), which show highly specific binding to the cap structure, m⁷G(5′)ppp(5′)N. Two major cap-binding activities have been characterized in eukaryotes. The first is the nuclear cap-binding complex (CBC), which plays a role in pre-mRNA splicing (1-3), polyadenylation (4), and U small nuclear RNA (snRNA) export (5). The second, eIF4E (6), is part of a trimeric complex, eIF4F, which is required for cap-dependent translation of mRNA.

 CBC was initially identified in nuclear extracts from HeLa cells as an activity that bound specifically to a normal 7-methyl guanosine-5′-capped RNA. Purification of the activity showed that it was a heterodimeric complex comprising two subunits; CBP80 and CBP20 (1). Neither protein alone can bind specifically to the 5′cap—only as a heterodimer. Current evidence has shown that CBC is required for efficient (1) pre-mRNA splicing, (2) polyadenylation, and (3) the export of RNA polymerase II–transcribed U snRNA.

CBC is required for efficient splicing of the cap-proximal intron, where its major function is to facilitate the binding of U1 snRNP to the cap-proximal 5′ splice site (3). Experiments in the yeast Saccharomyces cerevisiae and in HeLa splicing extracts have demonstrated that this function of CBC is conserved in evolution (2, 7).

A role for CBC in polyadenylation has also been demonstrated in vitro (4). Depletion of CBC from HeLa cell polyadenylation extracts results in a reduction in the efficiency of polyadenylation. Further analysis of this defect demonstrated that CBC was required for efficient cleavage of the pre-mRNA, but not for the polyadenylation reaction itself.

Nucleocytoplasmic transport of some classes of RNA, specifically the 5′capped uracil-rich (U(snRNAs, is facilitated by CBC. Antibodies raised against one of the subunits, CBP20, can specifically inhibit the interaction of CBC with the cap and, as a consequence, inhibit the export of these U snRNAs from the nucleus to the cytoplasm (5).

The other CBP, eIF4E, is required for cap-dependent translation of mRNA in the cytoplasm, and it can bind directly to the cap as a monomer (6). In order to function in translation, eIF4E has to assemble with two other polypeptide chains in a heterotrimeric complex of eIF4A, eIF4G, and eIF4E, to form a complex known as eIF4F. This trimeric complex binds to the cap of mRNAs and complexes with a second translational initiation complex, eIF3, which has an RNA helicase activity. This helicase activity is thought to unwind secondary structure in the mRNA and to allow the cap-dependent association of the 40S ribosomal subunit with the mRNA. The 40S subunit then scans for the initiation codon complexes with the 60S ribosomal subunit to initiate translation.

References

1.E. Izaurralde, J. Lewis, C. McGuigan, M. Jankowska, E. Darzynkiewicz, and I. Mattaj (1994(Cell 78, 657–668. 

2.J. Lewis, D. Görlich, and I. Mattaj (1996) Nucl. Acids Res, 24, 3332–3336. 

3.J. D. Lewis, E. Izaurralde, A. Jarmolowski, C. McGuigan, and I. W. Mattaj (1996) Genes Devel. 10,  1683-1693 .

4. S. M. Flaherty, P. Fortes, E. Izaurralde, I. W. Mattaj, and G. M. Gilmartin (1997) Proc. Nat. Acad. Sci. USA 94, 11893–11898. 

5. E. Izaurralde, J. Lewis, C. Gamberi, A. Jarmolowski, C. McGuigan, and I. W. Mattaj (1995(Nature 376, 709–712. 

6. N. Sonnenberg, M. Rupprecht, W. Merrick, and A. Shatkin (1979) Proc. Natl. Acad. Sci. USA 75, 4349-4345.

7. H. Colot, F. Stutz, and M. Rosbash (1996) Genes Devel. 10, 1699–1708.

اخر الاخبار

اخبار العتبة العباسية المقدسة

العتبة العباسية المقدسة تواصل تنظيم مجالس العزاء الصباحية بذكرى زيارة عاشوراء

مواكب العزاء تستذكر في التاسع من شهر المحرم شهادة عبدالله الرضيع بن الحسين (عليهما السلام)

العتبة العباسية المقدسة تستذكر تضحيات القاسم بن الحسن (عليهما السلام)

شعبة الحرم الشريف تواصل تنفيذ خطتها الخاصة بشهر المحرّم داخل مرقد أبي الفضل العباس (عليه السلام)

المزيد

الآخبار الصحية

لهذا السبب.. إغلاق 25 مركزًا لعلاج الإدمان في مصر ؟

خلافا للاعتقاد الشائع.. علماء يكشفون أسرار بذور البطيخ ؟!

هذا ما يحدث لجسمك عند تناولك الطماطم بانتظام !

تعرف على أطعمة تسرّع "تعافي الجسم" من حروق الشمس

المزيد

الآخبار التكنلوجية

الثلوج تغطي الصحراء الأكثر جفافا في العالم!

بتلسكوب "ألما".. التقاط صورا غير مسبوقة لبدايات الكون !

هل هاتفك مراقب؟.. 5 علامات خطيرة تكشف التجسس عليك

دبي تطلق أول رحلة تجريبية للتاكسي الجوي

المزيد

مواضيع ذات صلة

Other Attenuated Systems: Operons, Bacillus subtilis and HIV

Coupling Translation to Termination

trp Multiple Secondary Structures in trp Leader RNA

Early Explorations of the Hypersynthesis

The Serendipitous Discovery of trp Enzyme Hypersynthesis

Rapid Induction Capabilities of the trp Operon

The Aromatic Amino Acid Synthetic Pathway and its Regulation

How AraC Protein Loops and Unloops

DNA Looping and Repression of araBAD

Binding Sites of the ara Regulatory Proteins

Endoplasmic Reticulum-Associated Degradation and the Unfolded Protein Response

Protein Folding and Modifications in the Endoplasmic Reticulum