ROLE OF CAP FUNCTION DURING EUKARYOTIC PROTEIN SYNTHESIS AND PRECURSOR MESSENGER-RNA SPLICING

Important note: Information in this article was accurate in 1990. The state of the art may have changed since the publication date.

ROLE OF CAP FUNCTION DURING EUKARYOTIC PROTEIN SYNTHESIS AND PRECURSOR MESSENGER-RNA SPLICING

Diss Abstr Int [B]; 50(4):1199 1989. Unique Identifier : AIDSLINE ICDB/90659915
Edery I; McGill Univ., Canada

Abstract: The cap structure, m7GpppX (where X = any nucleotide), is present at the 5' end of all eukaryotic cellular messenger RNAs (except organellar). Previous studies have demonstrated that during protein synthesis the cap structure is recognized by a approx 24 kD cap binding protein (CBP), termed eukaryotic initiation factor 4E (eIF-4E). With the use of a newly developed cap-analogy affinity matrix a high molecular weight complex that contains eIF-4E was purified, termed eIF-4F. In addition to eIF-4E this CBP complex consists of eIF-4A and a 220 kD polypeptide (p220). Using an RNA unwinding assay direct evidence was obtained indicating that eIF-4F, eIF-4A and eIF-4B functionally interrelate resulting in helicase activity. Secondary structure in the 5' untranslated region of eukaryotic mRNAs inhibits translation, therefore this unwinding activity is most likely required for efficient 40S ribosomal subunit attachment to mRNA. To facilitate the purification and biophysical characterization of eIF-4E, the yeast homolog was overexpressed in E coli. mRNA secondary structure can also inhibit translation in trans by another mechanism. This was shown for the unique structure (TAR) at the 5' end of all mRNAs from the human immunodeficiency virus-1 (HIV-1). The mechanism of translation inhibition involves the activation of the double-stranded RNA dependent kinase (dsI), which catalyzes the phosphorylation of eIF-2. This is the first demonstration of a specific naturally occurring mRNA sequence that can activate dsI. A novel translational regulatory mechanism is proposed. Finally, the cap structure is also required for efficient precursor mRNA splicing in HeLa nuclear extracts. These and other studies indicate that the cap structure plays a multifunctional role during regulation of gene expression.

Keywords: Gene Expression/PHYSIOLOGY Hela Cells Human Proteins/*BIOSYNTHESIS RNA Caps/*PHYSIOLOGY RNA Precursors/*GENETICS RNA Splicing/*PHYSIOLOGY RNA, Messenger/*GENETICS THESIS
900630
M9060643

AEGiS is a 501(c)3, not-for-profit, tax-exempt, educational corporation. AEGiS is made possible through unrestricted funding from Boehringer Ingelheim, Bridgestone/Firestone Charitable Trust, Bristol-Myers Squibb Company, Elton John AIDS Foundation, Gill Foundation, the National Library of Medicine, Quest Diagnostics, Roche and Trimeris, and donations from users like you. Always watch for outdated information. This article first appeared in 1990. This material is designed to support, not replace, the relationship that exists between you and your doctor.

AEGiS presents published material, reprinted with permission and neither endorses nor opposes any material. All information contained on this website, including information relating to health conditions, products, and treatments, is for informational purposes only. It is often presented in summary or aggregate form. It is not meant to be a substitute for the advice provided by your own physician or other medical professionals. Always discuss treatment options with a doctor who specializes in treating HIV.

Copyright ©1980, 1990. AEGiS. All materials appearing on AEGiS are protected by copyright as a collective work or compilation under U.S. copyright and other laws and are the property of AEGiS, or the party credited as the provider of the content. .