Leaky scanning

Leaky scanning is a phenomenon in which a weak initiation codon triplet on the mRNA is sometimes skipped by the ribosome during translation initiation. The ribosomal subunit 40S continues scanning to another initiation codon. The weak initiation codon can be an ACG or an ATG in a weak Kozak consensus context.
In this way, one mRNA can code for several different proteins if the AUG are not in frame, or for proteins with different N-termini if the AUG are in the same frame.

Upstream ORFs (uORF) are small coding regions preceding an ORF, The latter must be translated by leaky scanning or termination-reinitiation. Many eukaryotic genes encode for uORF to downregulate the translation/mRNA ratio of a gene. These genes are described in the uORF database
The leaky scanning is favored in case of cellular stress in which EIF2alpha is phosphorylated , like in case of dsRNA/PKR activation. Many eukaryotic stress response genes are under the transcription control of a uORF. Viruses may use this regulatory system for their own purpose.

Family	Host	Genus	Virus	Products	RefSeq	Ref.
Bunyaviridae		Orthobunyavirus	Bunyamwera virus	NS/NSs	NC_001927	Bunyavirus nucleoprotein, N, and a non-structural protein, NSS, are coded by overlapping reading frames in the S RNA F Fuller, A S Bhown, D H Bishop J. Gen. Virol. August 1983; 64 (Pt 8): 1705?1714
		Hantavirus	Andes virus	NS/NSs	NC_003466	The Andes hantavirus NSs protein is expressed from the viral small mRNA by a leaky scanning mechanism Jorge Vera-Otarola, Loretto Solis, Ricardo Soto-Rifo, Emiliano P Ricci, Karla Pino, Nicole D Tischler, Th?ophile Ohlmann, Jean-Luc Darlix, Marcelo L?pez-Lastra J. Virol. February 2012; 86: 2176?2187
		Phlebovirus	Rift valley fever virus	NSm-Gn, NSm, NSm'	NC_014396	The Rift Valley fever accessory proteins NSm and P78/NSm-GN are distinct determinants of virus propagation in vertebrate and invertebrate hosts Felix Kreher, Carole Tamietti, C?line Gommet, Laurent Guillemot, Myriam Ermonval, Anna-Bella Failloux, Jean-Jacques Panthier, Mich?le Bouloy, Marie Flamand Emerg Microbes Infect October 2014; 3: e71
Caliciviridae		Norovirus	Murine norovirus	ORF4/CP	NC_008311	Norovirus regulation of the innate immune response and apoptosis occurs via the product of the alternative open reading frame 4 Nora McFadden, Dalan Bailey, Guia Carrara, Alicia Benson, Yasmin Chaudhry, Amita Shortland, Jonathan Heeney, Felix Yarovinsky, Peter Simmonds, Andrew Macdonald, Ian Goodfellow PLoS Pathog. December 2011; 7: e1002413
Hepadnaviridae		Orthohepadnavirus	Hepatitis B virus	HBeAg/C/P	NC_003977	Translation of the first upstream ORF in the hepatitis B virus pregenomic RNA modulates translation at the core and polymerase initiation codons Augustine Chen, Y F Kao, Chris M Brown Nucleic Acids Res. 2005; 33: 1169?1181
				M/S?	NC_003977
Hepeviridae		Hepevirus	Hepatitis E virus	ORF3/CP	NC_001434	The open reading frame 3 gene of hepatitis E virus contains a cis-reactive element and encodes a protein required for infection of macaques Judith Graff, Hanh Nguyen, Claro Yu, William R Elkins, Marisa St Claire, Robert H Purcell, Suzanne U Emerson J. Virol. June 2005; 79: 6680?6689
Herpesviridae		Simplexvirus	Human herpesvirus 1	uORF/UL30	NC_001806	Translational regulation of herpes simplex virus DNA polymerase D R Yager, A I Marcy, D M Coen J. Virol. May 1990; 64: 2217?2225
		Cytomegalovirus	Human cytomegalovirus	uORF2/gp74	NC_006273	Translational inhibition by a human cytomegalovirus upstream open reading frame despite inefficient utilization of its AUG codon J Cao, A P Geballe J. Virol. February 1995; 69: 1030?1036
		Rhadinovirus	Kaposi's sarcoma-associated herpesvirus	uORF1+ORF35/ uORF28+ORF36	NC_009333	Dual short upstream open reading frames control translation of a herpesviral polycistronic mRNA Lisa M Kronstad, Kevin F Brulois, Jae U Jung, Britt A Glaunsinger PLoS Pathog. January 2013; 9: e1003156
Orthomyxoviridae		Influenza virus A	A/Puerto Rico/8/34	PB1/PN1-F2/N40	NC_002021	A novel influenza A virus mitochondrial protein that induces cell death W Chen, P A Calvo, D Malide, J Gibbs, U Schubert, I Bacik, S Basta, R O?Neill, J Schickli, P Palese, P Henklein, J R Bennink, J W Yewdell Nat. Med. December 2001; 7: 1306?1312 A complicated message: Identification of a novel PB1-related protein translated from influenza A virus segment 2 mRNA Helen M Wise, Agnes Foeglein, Jiechao Sun, Rosa Maria Dalton, Sheetal Patel, Wendy Howard, Emma C Anderson, Wendy S Barclay, Paul Digard J. Virol. August 2009; 83: 8021?8031
		Influenza virus B	B/Lee/1940	NB/NA	NC_002209	Effect of mutations and deletions in a bicistronic mRNA on the synthesis of influenza B virus NB and NA glycoproteins M A Williams, R A Lamb J. Virol. January 1989; 63: 28?35
Papillomaviridae		Alphapapillomavirus	HPV16	E6/E7	NC_001526	Leaky scanning is the predominant mechanism for translation of human papillomavirus type 16 E7 oncoprotein from E6/E7 bicistronic mRNA S N Stacey, D Jordan, A J Williamson, M Brown, J H Coote, J R Arrand J. Virol. August 2000; 74: 7284?7297
Polyomaviridae		Polyomavirus	SV40	Agno/VP2/VP3?	NC_001669
Paramyxoviridae		Aquaparamyxovirus	Sendai virus	P/C	EU156171
		Respirovirus	Sendai virus	C'/P/C/Y1/Y2	NC_001552	Sendai virus contains overlapping genes expressed from a single mRNA C Giorgi, B M Blumberg, D Kolakofsky Cell December 1983; 35: 829?836
		Morbilivirus	Measles virus	P/C	NC_001498	Measles virus P gene codes for two proteins W J Bellini, G Englund, S Rozenblatt, H Arnheiter, C D Richardson J. Virol. March 1985; 53: 908?919
		Henipavirus	Hendra virus	P/C	NC_001906	Determination of the henipavirus phosphoprotein gene mRNA editing frequencies and detection of the C, V and W proteins of Nipah virus in virus-infected cells Michael K Lo, Brian H Harcourt, Bruce A Mungall, Azaibi Tamin, Mark E Peeples, William J Bellini, Paul A Rota J. Gen. Virol. February 2009; 90: 398?404
Reoviridae		Rotavirus	Rotavirus A	VP7.1/VP7.2,	NC_011503
				NSP5/NSP6	NC_011505	Expression of rotavirus proteins encoded by alternative open reading frames of genome segment 11 N M Mattion, D B Mitchell, G W Both, M K Estes Virology March 1991; 181: 295?304
		Orbivirus	Bluetongue virus	Vp6a, NS4	NC_006008	Detection of a fourth orbivirus non-structural protein Mourad Belhouchet, Fauziah Mohd Jaafar, Andrew E. Firth, Jonathan M. Grimes, Peter P. C. Mertens, Houssam Attoui PLoS ONE 2011; 6: e25697
				NS3a	NC_006015
		Orthoreovirus	Mammalian orthoreovirus	Sigma1/sigma1s	NC_004277	Reovirus hemagglutinin mRNA codes for two polypeptides in overlapping reading frames H Ernst, A J Shatkin Proc. Natl. Acad. Sci. U.S.A. January 1985; 82: 48?52
				MuNS/MuNSC	NC_004281	Avian and mammalian reoviruses use different molecular mechanisms to synthesize their {micro}NS isoforms Lisa K Busch, Javier Rodr?guez-Grille, J Ignacio Casal, Jos? Mart?nez-Costas, Javier Benavente J. Gen. Virol. November 2011; 92: 2566?2574
Coronaviridae		Betacoronavirus	Bovine coronavirus	N/I	NC_003045	The nucleocapsid protein gene of bovine coronavirus is bicistronic S D Senanayake, M A Hofmann, J L Maki, D A Brian J. Virol. September 1992; 66: 5277?5283
Arteriviridae		Arterivirus	Equine arteritis virus	E/GP2	NC_002532	Identification of a novel structural protein of arteriviruses E J Snijder, H van Tol, K W Pedersen, M J Raamsman, A A de Vries J. Virol. August 1999; 73: 6335?6345
				ORF5a/GP5	NC_002532	Discovery of a small arterivirus gene that overlaps the GP5 coding sequence and is important for virus production Andrew E Firth, Jessika C Zevenhoven-Dobbe, Norma M Wills, Yun Young Go, Udeni B R Balasuriya, John F Atkins, Eric J Snijder, Clara C Posthuma J. Gen. Virol. May 2011; 92: 1097?1106
Alphatetraviridae		Omegatetravirus	Helicoverpa armigera stunt virus	P17/CP	NC_004060	Sequence of RNA2 of the Helicoverpa armigera stunt virus (Tetraviridae) and bacterial expression of its genes T N Hanzlik, S J Dorrian, K N Johnson, E M Brooks, K H Gordon J. Gen. Virol. April 1995; 76 ( Pt 4): 799?811
Baculoviridae		Alphabaculovirus	Autographa californica multiple nucleopolyhedrovirus	uORF/gp64	NC_004323	Baculovirus gp64 gene expression: negative regulation by a minicistron M J Chang, G W Blissard J. Virol. October 1997; 71: 7448?7460
Alphaflexviridae		Potexvirus	Potato virus X	TGB2/TGB3	NC_011620	In vivo translation of the triple gene block of potato virus X requires two subgenomic mRNAs J Verchot, S M Angell, D C Baulcombe J. Virol. October 1998; 72: 8316?8320
Caulimoviridae		Tungrovirus	Rice tungro bacilliform virus	ORF1/ORF2/ORF3	NC_001914	Rice tungro bacilliform virus open reading frames II and III are translated from polycistronic pregenomic RNA by leaky scanning J F?tterer, H M Rothnie, T Hohn, I Potrykus J. Virol. October 1997; 71: 7984?7989
Luteoviridae		Luteovirus	Barley yellow dwarf virus	P3a/CP/MP	NC_004750	Control of start codon choice on a plant viral RNA encoding overlapping genes S P Dinesh-Kumar, W A Miller Plant Cell June 1993; 5: 679?692 Discovery of a Small Non-AUG-Initiated ORF in Poleroviruses and Luteoviruses That Is Required for Long-Distance Movement Ekaterina Smirnova, Andrew E. Firth, W. Allen Miller, Dani?le Scheidecker, V?ronique Brault, Catherine Reinbold, Aur?lie M. Rakotondrafara, Betty Y.-W. Chung, V?ronique Ziegler-Graff PLoS Pathog. May 2015; 11: e1004868
		Polerovirus	Potato leafroll virus	P0/P1	NC_001747	Nucleotide sequence of potato leafroll luteovirus RNA M A Mayo, D J Robinson, C A Jolly, L Hyman J. Gen. Virol. May 1989; 70 ( Pt 5): 1037?1051
				P3a/CP/MP	NC_001747	Characterization of a potato leafroll luteovirus subgenomic RNA: differential expression by internal translation initiation and UAG suppression E Tacke, D Pr?fer, F Salamini, W Rohde J. Gen. Virol. October 1990; 71 ( Pt 10): 2265?2272 Discovery of a Small Non-AUG-Initiated ORF in Poleroviruses and Luteoviruses That Is Required for Long-Distance Movement Ekaterina Smirnova, Andrew E. Firth, W. Allen Miller, Dani?le Scheidecker, V?ronique Brault, Catherine Reinbold, Aur?lie M. Rakotondrafara, Betty Y.-W. Chung, V?ronique Ziegler-Graff PLoS Pathog. May 2015; 11: e1004868
		Enamovirus	Pea enation mosaic virus	P0/P1	NC_003629
Tombusviridae		Aureusvirus	Pothos latent virus	MP/P14	NC_000939	Molecular analysis of the pothos latent virus genome L Rubino, M Russo J. Gen. Virol. June 1997; 78 ( Pt 6): 1219?1226
		Machlomovirus	Maize chlorotic mottle virus	ORF1/ORF2	NC_003627
Unassigned		Sobemovirus	Southern bean mosaic virus	MP/X/ORF2A	NC_004060	An essential fifth coding ORF in the sobemoviruses Roger Ling, Adrienne E Pate, John P Carr, Andrew E Firth Virology November 2013; 446: 397?408
Tymoviridae		Tymovirus	Turnip yellow mosaic virus	MVP/ORF1	NC_004063	Infectious TYMV RNA from cloned cDNA: effects in vitro and in vivo of point substitutions in the initiation codons of two extensively overlapping ORFs J J Weiland, T W Dreher Nucleic Acids Res. June 26, 1989; 17: 4675?4687
Virgaviridae		Hordeivirus	Barley stripe mosaic virus	TGB2/TGB3	NC_003481	Expression of the barley stripe mosaic virus RNA beta ?triple gene block? H Zhou, A O Jackson Virology February 15, 1996; 216: 367?379
		Pecluvirus	Peanut clump virus	CP/P39	NC_003668	Translation of the second gene of peanut clump virus RNA 2 occurs by leaky scanning in vitro E Herzog, H Guilley, C Fritsch Virology April 1, 1995; 208: 215?225
				TGB2/TGB3