Leaky scanning

The mRNA of eucaryotes does not possess specific initiation sequences. Rather, the AUG start codon is identified by scanning the eucaryotic mRNA the 408 subunit of the ribosome threads the 5 non-translated end of the mRNA and uses the first AUG codon encoimtered to initiate translation. Whether a AUG codon is used as an initiator depends, additionally, upon the sequence context. If the sequence environment is unfavorable for initiation, then the scanning is continued and initiation occurs at one of the next AUG. With the help of this leaky scanning" strategy it is possible to produce proteins with different N-termini from the same mRNA. 8ince there are often signal sequences foimd at the N-terminus, this mechanism may lead to alternative com-partmentalization of a protein. 

Importantly, inhibition of translation via phosphorylation by the eIF2a kinases can have both a general and a gene-specific effect and can even lead to enhanced translation of specific mRNAs. Whereas the general level of translation maybe reduced under these conditions, specific mRNAs are preferentially translated. This upregulation of specific mRNAs is explained by a leaky scanning of AUG codons and the use of alternative initiation sites. 

Despite the importance of alternative splicing for the diversity of the proteome and regulation of gene expression two aspects of protein-coding mRNAs— alternative translation initiation and short peptides—have not yet been touched upon. Alternative translation initiation can generate from one transcript two or more protein isoforms. In the case of leaky scanning the ribosome bypasses the... 

About 6% (2218) of the complete isoform protein set ftp //fantom.gsc.riken.jp/ RTPS/fantom3 mouse/predkted rtps/IP) entries are shorter than 100 aa. However the majority of these peptides (50-100aa), including antimicrobial peptides and neurohormones, are considerable longer (Frith et al 2006) than known endogenously encoded short peptides of 7—30 aa that are often tumour T-cell epitopes. These peptides appear to be produced by leaky-scanning (TRPl) (Wang et al 1996), IRES or perhaps from tissue cell-specific alternative splice variants (M-CSF) (Probst-Kepper et al 2001). Since the peptides were identified in tumour cell lines and not characterized beyond T-cell epitope level, their presence and function in normal cells is less clear. 

Polar Cell Systems for Membrane Transport Studies Direct current electrical measurement in epithelia steady-state and transient analysis, 171, 607 impedance analysis in tight epithelia, 171, 628 electrical impedance analysis of leaky epithelia theory, techniques, and leak artifact problems, 171, 642 patch-clamp experiments in epithelia activation by hormones or neurotransmitters, 171, 663 ionic permeation mechanisms in epithelia biionic potentials, dilution potentials, conductances, and streaming potentials, 171, 678 use of ionophores in epithelia characterizing membrane properties, 171, 715 cultures as epithelial models porous-bottom culture dishes for studying transport and differentiation, 171, 736 volume regulation in epithelia experimental approaches, 171, 744 scanning electrode localization of transport pathways in epithelial tissues, 171, 792. 

Fig. 7 (a) Beads packing device working in a flow system, taking advantage of a leaky wall (reproduced from [27]) (with permission), (b) a scanning electron microscopy image of a flow through reactor composed of pillar made walls used to pack microspheres (reproduced from [28]) (with permission)... 

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