Linkage of Mls genes to endogenous mammary tumour viruses of inbred mice

WONITOR 1

A 'digest' of some recent papers of interest in the primary journals. A maternally inherited superantigen encoded by a mammarytumour virus 1'. MARRACK, E. KI,rSHNIR AND J. KAPPLER

Nature 349, 524-526

Linkage of Mls genes to endogenous mammary tumour viruses of inbred mice W.N. FRANKEI., C. RIP,',, J.M. COFFIN AND B.a. Ht-BER

Nature 349, ~26---528

An endogenous retrovirus mediating deletion of a~ T cells? D.L. WOODLAND, M.P. HAPP, KJ. GOLLOB AND E. PALMER

Nature 349, 529-530

Genes encoding ligands for deletion of V~ll T cells cosegregate with mammary tumour virus genomes P.J. DYSON ETAL.

Nature349, 531-532

The

minor

lymphocyte

stimulating

Mls genes are so named because their

Mutational analysis of an archaebacterial promoter: essential role of a TATAbox for transcription efficiency and start-site selection W-D. R1ETER, U. HUI)EPOHL AND W. ZILLIG

Proc. Natl Acad. Sci. USA 87, 9505-9513

Simple distinctions between 'prokaryotic-type' and 'eukaryotic-type' transcriptional promoters no longer appear to be valid. By careful mutational analysis of the 16S/23S rRNAencoding promoter from the archaebacterium Sul]blobus sp. B12, Rieter et aL have demonstrated that this promoter resembles eukaryotic RNA polymerase II (and TATA-containing RNA polymerase III) promoters rather than the promoters of eubacteria

Retron for the 67-base multicopy single-stranded DNAfrom Eschericbia coil: a potential transposable element encoding both reverse transcriptase and Dam methylase functions M-Y. HSU, M. INOUYE AND S. INOUYE

Proc. Natl Acad. Sci+ USA 87, 9454-9458

The clinical isolate Cl-1 of E. coil carries a bizarre DNA-RNA hybrid molecule (msDNA-Ec67), comprising a 67 base multicopy single-stranded DNA linked at its 5' end to the 2'-OH of the 15th G residue of a 58 base RNA through a 2',5'-phosphodiester linkage. Interestingly, reverse transcription is required for msDNA synthesis; an RNA transcript is thought to form a secondary structure that acts

]

products are extremely powerful stimulatory antigens in mixed lymphocyte cultures, even w h e n the cells carry identical major histocompatibility complexes (MHCs). Mls products are believed to bypass the usual ligandbinding groove of class II MHC molecules; a particular Mls molecule binds simultaneously to an MHC class I1 molecule and a T-cell receptor carlying a characteristic V[3 chain. In vivo, this effect is manit}ested by the deletion in the thymus of T cells that carry receptors including the V[8 chain that interacts with the Mls molecule. Four papers recently published in Nature indicate, rather surprisingly, that the Mls genes are in fact e n d o g e n o u s retroviral genes - in all cases reported here belonging to the mouse nlammary turnout virus (MMTV) family. Marrack et al. have discovered a novel mouse Mls molecule that was maternally inherited, by passage from

mother to offspring in milk: the characteristic T-cell clonal deletion was abolished w h e n mice were cured of mouse ntammary tumour virus (MMTV) transmission b\ fl~ster nur,,ing. The three other papers involved more classical genetic approact~es: clonal deletion, in vitro stimu[atiot~ consistently mapped to endogen~us retroviral genomes. ~ b o d l a n d el al also s h o w e d that stimulating cells ex pressed the viral transcript, but genet ically identical ones that did not express viral transcripts dkl not stitn ulate. Marrack et al. suggest that sequences in the long terminal repeat may encode the Mls antigen. One is left with the problenl ¢)1 explaining the existence and be haviour of these sequences. P(/ssi bilities include the idea thai the virus may be trying to activate T cells that are then ripe for infection, and the response of the mouse is to delete all such possible target cells. ~'~

such as E. coil Thus, deletion and linker-substitution mutagenesis identified a core promoter b e t w e e n nucleotides -38 and -2 front the transcriptional start site. This core region could be dissected into distal and proximal elements (DPE and PPE) between -38 and -25, and between -11 and -2. respectively. All mutations within the DPE, which contains an AT-rich sequence conserved a m o n g archaebacterial promoters, drastically reduced transcription in an in vitro assay, and interfered with start site selection. Inactivation of the PPE, which is also Nl'-rich, required more extensive inutagenesis. Mutations at or around the TGC start codon led to nmltiple

start sites, but had little effect on transcriptional efficiency. These fea tures, particularly the requirement for AT-rich promoter elements, resetnl)lc the properties of eukawotic p~>iynterase 11 promoters and distinguish the archaebacterial promoter + froth typical eubacterial promoter~,. The eubacterial -3-% and -10 promoter elements have no sequence similarity with the archaebacterial promoter elements, and it is their -10 element that controls start site selection, in contast to the more upstrcaln 1o cation of the archaebacterial l)PE. This study provides further supp(>rt f+:+r a ( ' ( ) l n n / ( ) l l evoh~tionat T t+rigin +q archaebacterial and eukarvotic R'X~ polymerases. /:

as a template and primer for msDNA synthesis by reverse transcriptase (RT). The RT gene has been identi fled, in the region encoding the RNA and DNA components of msI)NA. The msDNA-synthesizing system could be evolutionarily related to retrotransposons/retroviruses: hence the designation retron, ttsu et a[. have m a p p e d a 34 kb DNA fragment containing retron-Ec67 to the equivalent of 19 rain on the E. coil K-12 map. This fragment is flanked by a 26 bp direct repeat, suggesting that it inte grated by a mechanism akin to transposition or phage integration. The sequence of a 7.4 kb segment of retron-gc67 revealed five large o p e n reading frames (ORFs); one encodes

RT, and one is clcarlx tclatt:d h~ I)ztm methylase, which meth\latc', (~:\lI sites. The ORF product b, a genuine Illethvlitse, irl Ill:It it c/tt3 c{+Illplct!lc!~t Dam strains, although it is less acti\c than 'conventional' Dam meth\-Ia'~c The sequenced region has i~inc smaller ORFs Ibetween 100 at>_t 2/~i~ residues): t\~o (>f the OREs yCbCIIII/IL gene I)roducts of the P2-type phage 186 (the cl and c p : 6 gene products! Whatever the mechanism b \ \~hi<>n, and three ~,}Xl( ,, arc ~lu~,tcred iil ',he l)[¢)Ill¢)t,~:l l,..:~i~l <>{"the RT gcnc~ ,~cll~_l it }>c kli++~d,+,.¢] ill ~ontiol <)t thi> clement t(,t~? /

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