mitochondrial translation

[ValWood]

mitochondria large subunit

Systematic ID	Gene name	Product description	Budding yeast orthologs	Human orthologs
SPAC1610.02c	mrpl1	mitochondrial ribosomal protein subunit L1	MRPL1	MRPL1
SPAC31A2.03	mrp11	mitochondrial ribosomal protein subunit L10	MRPL11	MRPL10
SPAC1486.07c	mrpl19	mitochondrial ribosomal protein subunit L11	MRPL19	MRPL11
SPCC4B3.09c	mrpl12	mitochondrial ribosomal protein subunit L12	MNP1	MRPL12
SPBC16G5.04	mrpl23	mitochondrial ribosomal protein subunit L13	MRPL23	MRPL13
SPBC887.07	mrpl38	mitochondrial ribosomal protein subunit L14	MRPL38	MRPL14
SPBC9B6.06	mrpl10	mitochondrial ribosomal protein subunit L15	MRPL10	MRPL15
SPBC1105.03c	mrpl16	mitochondrial ribosomal protein subunit L16	MRPL16	MRPL16
SPBC1271.13	mrpl8	mitochondrial ribosomal protein subunit L17	MRPL8	MRPL17
SPAC343.02	img1	mitochondrial ribosomal protein subunit L19	IMG1	MRPL19
SPCC16C4.15	rml2	mitochondrial ribosomal protein subunit L2	RML2	MRPL2
SPBP4H10.15	aco2	mitochondrial ribosomal protein subunit L21/aconitate hydratase, fusion protein	ACO2,MRPL49	ACO2
SPCC1739.02c	mrpl22	mitochondrial ribosomal protein subunit L22	MRPL22	MRPL22
SPAC31A2.08	mrp20	mitochondrial ribosomal protein subunit L23	MRP20	MRPL23
SPAC4F8.02c	mrpl40	mitochondrial ribosomal protein subunit L24	MRPL40	MRPL24
SPAP19A11.05c	mrp7	mitochondrial ribosomal protein subunit L27	MRP7	MRPL27
SPBC14C8.10	mrpl24	mitochondrial ribosomal protein subunit L28	MRPL24	MRPL28
SPCC4G3.06c	mrpl4	mitochondrial ribosomal protein subunit L29	MRPL4	MRPL47
SPAC644.17c	mrpl9	mitochondrial ribosomal protein subunit L3	MRPL9	MRPL3
SPCC1919.08c	mrpl33	mitochondrial ribosomal protein subunit L30	MRPL33	MRPL30
SPBC1711.18	tam9	mitochondrial ribosomal protein subunit L31	MRPL36	MRPL55
SPBC1604.13c	mrpl32	mitochondrial ribosomal protein subunit L32	MRPL32	MRPL32
SPBC4F6.08c	mrpl39	mitochondrial ribosomal protein subunit L33	MRPL39	MRPL33
SPBC21C3.04c	mrx14	mitochondrial ribosomal protein subunit L34	MRX14	MRPL34
SPBC8D2.23	new15	mitochondrial ribosomal protein subunit L35	MRP35	MRPL35
SPBC83.06c	rtc6	mitochondrial ribosomal protein subunit L36	RTC6	MRPL36
SPBC2F12.10	mrpl35	mitochondrial ribosomal protein subunit L38	MRPL35	MRPL38
SPBC2D10.08c	yml6	mitochondrial ribosomal protein subunit L4	YML6	MRPL4
SPAC4F8.05c	mrpl28	mitochondrial ribosomal protein subunit L40	MRPL28	MRPL40
SPAC3A12.19	mrpl27	mitochondrial ribosomal protein subunit L41	MRPL27	MRPL41
SPBC19C2.12	mrpl51	mitochondrial ribosomal protein subunit L43	MRPL51	MRPL39,MRPL43
SPBC3B9.14c	mrpl3	mitochondrial ribosomal protein subunit L44	MRPL3	MRPL44
SPCC126.05c	mrpl17	mitochondrial ribosomal protein subunit L46	MRPL17	MRPL46
SPAC3H8.03	img2	mitochondrial ribosomal protein subunit L49	IMG2	MRPL49
SPBC2F12.02c	mrpl7	mitochondrial ribosomal protein subunit L5	MRPL7
SPCC24B10.04	mrpl50	mitochondrial ribosomal protein subunit L50	MRPL50	MRPL50
SPBC56F2.14	mrpl44	mitochondrial ribosomal protein subunit L53	MRPL44	MRPL53
SPCC645.09	mrpl37	mitochondrial ribosomal protein subunit L54	MRPL37	MRPL54
SPBC1539.01c	mrpl15	mitochondrial ribosomal protein subunit L57	MRPL15	MRPL57
SPCC1393.11	mrpl20	mitochondrial ribosomal protein subunit L58	MRPL20	NGRN
SPAC1952.14c	mrpl25	mitochondrial ribosomal protein subunit L59	MRPL25	GADD45GIP1
SPAC12G12.08	mrpl6	mitochondrial ribosomal protein subunit L6	MRPL6
SPCC16A11.11	mrpl31	mitochondrial ribosomal protein subunit L60	MRPL31
SPBC18H10.17c	mhr1	mitochondrial ribosomal protein subunit L67	MHR1
SPCC777.17c		mitochondrial ribosomal protein subunit L9		MRPL9
SPCC1442.19	mrp49	mitochondrial ribosomal protein subunit Mrp49	MRP49	MRPS25
SPAC589.11	pth4	mitochondrial translation release factor	PTH4	MRPL58

mitochondria small subunit

Systematic ID	Gene name	Product description	Budding yeast orthologs	Human orthologs
SPBC16A3.14		mitochondrial ribosomal protein subunit	MRP1,RSM26
SPBC3H7.04		mitochondrial ribosomal protein subunit	MRP1,RSM26
SPBC2G2.07c	mug178	mitochondrial ribosomal protein subunit L51-b	MRP51
SPAC23A1.18c	mrp51	mitochondrial ribosomal protein subunit L51-bS1m	MRP51	MRPS28
SPBC211.01	rsm10	mitochondrial ribosomal protein subunit S10	RSM10	MRPS10
SPAC1B3.18c	mrps18	mitochondrial ribosomal protein subunit S11	MRPS18	MRPS11
SPAC4F8.06	mrps12	mitochondrial ribosomal protein subunit S12	MRPS12	MRPS12
SPCC1795.07	sws2	mitochondrial ribosomal protein subunit S13	SWS2
SPAC23H3.07c	mrp2	mitochondrial ribosomal protein subunit S14	MRP2	MRPS14
SPBC11B10.04c	mrps28	mitochondrial ribosomal protein subunit S15	MRPS28	MRPS15
SPBC354.06	mrps16	mitochondrial ribosomal protein subunit S16	MRPS16	MRPS16
SPBC409.14c	mrps17	mitochondrial ribosomal protein subunit S17	MRPS17	MRPS17
SPCC18B5.04	rsm18	mitochondrial ribosomal protein subunit S18	RSM18	MRPS18A,MRPS18B,MRPS18C
SPAC1751.02c	rsm19	mitochondrial ribosomal protein subunit S19	RSM19
SPAC24C9.10c	mrp4	mitochondrial ribosomal protein subunit S2	MRP4	MRPS2
SPBC839.09c	mrp21	mitochondrial ribosomal protein subunit S21	MRP21	MRPS21
SPBC16A3.04	rsm25	mitochondrial ribosomal protein subunit S23	RSM25	MRPS23
SPBC19F8.05	mrps26	mitochondrial ribosomal protein subunit S26	PET123	MRPS26
SPBC29A3.15c	rsm23	mitochondrial ribosomal protein subunit S29	RSM23	DAP3
SPMIT.08	var1	mitochondrial ribosomal protein subunit S3	VAR1	MRPS24
SPBC30D10.12c	rsm27	mitochondrial ribosomal protein subunit S33	RSM27	MRPS33
SPAC2F7.15	rsm24	mitochondrial ribosomal protein subunit S35	RSM24	MRPS35
SPAC24C9.13c	mrp10	mitochondrial ribosomal protein subunit S37	MRP10	CHCHD1
SPBC13G1.01c	nam9	mitochondrial ribosomal protein subunit S4	NAM9
SPBC4B4.11	fyv4	mitochondrial ribosomal protein subunit S41	FYV4
SPBC14C8.16c	bot1	mitochondrial ribosomal protein subunit S45	MRPS35
SPBC2D10.09	snr1	mitochondrial ribosomal protein subunit S47/3-hydroxyisobutyryl-CoA hydrolase Snr1	EHD3	HIBCH
SPAC4G9.17c	mrp5	mitochondrial ribosomal protein subunit S5	MRPS5	MRPS5
SPAC343.08c	mrp17	mitochondrial ribosomal protein subunit S6	MRP17	MRPS6
SPAC16E8.10c	rsm7	mitochondrial ribosomal protein subunit S7	RSM7	MRPS7
SPCC736.10c	mrps8	mitochondrial ribosomal protein subunit S8	MRPS8
SPAC29A4.03c	mrps9	mitochondrial ribosomal protein subunit S9	MRPS9	MRPS9

[hattrill]

Just updated our mitochondrial ribosome gene groups with Steven's help. Will add them once I've got a handle on the OXPHOS assembly factors

[ValWood]

mitochondrial tRNA ligases

Systematic ID	Gene name	Product description	Budding yeast orthologs	Human orthologs
SPAC23C11.09	ala1	mitochondrial and cytoplasmic alanine-tRNA ligase Ala1	ALA1	AARS1,AARS2
SPBC25B2.09c	mrs1	mitochondrial and cytoplasmic arginine-tRNA ligase Rrs1/Mrs1	MSR1,YDR341C	RARS2
SPAC3F10.03	grs1	mitochondrial and cytoplasmic glycine-tRNA ligase Grs1	GRS1,GRS2	GARS1
SPBC2G2.12	hrs1	mitochondrial and cytoplasmic histidine-tRNA ligase Hrs1	HTS1	HARS1,HARS2
SPBC1198.10c	slm5	mitochondrial asparagine-tRNA ligase Slm5	SLM5	NARS2
SPCC736.06	dar2	mitochondrial aspartate-tRNA ligase Dar2	MSD1	DARS2
SPAPB1A10.11c	mse1	mitochondrial glutamyl-tRNA ligase Mse1	MSE1	EARS2
SPCC18B5.08c	ism1	mitochondrial isoleucine-tRNA ligase	ISM1	IARS2
SPAC4G8.09		mitochondrial leucine-tRNA ligase	NAM2	LARS2
SPCC18.08	msk1	mitochondrial lysine-tRNA ligase Msk1	MSK1	KARS1
SPAC27E2.06c	msm1	mitochondrial methionine-tRNA ligase Msm1	MSM1	MARS2
SPCC736.03c	msf1	mitochondrial phenylalanyl-tRNA synthetase Msf1	MSF1	FARS2
SPBC24C6.03		mitochondrial proline-tRNA ligase	AIM10	PARS2
SPAC25B8.06c	dia4	mitochondrial serine-tRNA ligase	DIA4	SARS2
SPAC24C9.09		mitochondrial threonine-tRNA ligase	MST1	TARS2
SPAC3G9.13c	msw1	mitochondrial tryptophan-tRNA ligase Msw1	MSW1	WARS2
SPCC576.06c		mitochondrial tyrosine-tRNA ligase	MSY1	YARS2
SPAC4A8.08c	vrs2	mitochondrial valine-tRNA ligase Vrs2/Vas2	VAS1	VARS2

Not that tRNA ligases are a bit random. Sometimes there is one for each location (cytosol and mitochondrion), and sometimes there is a signal peptide which is sometimes cleaved and sometimes not.

[ValWood]

The rest of mitochondrial translation (without tRNAs)

• [ ]. split this table into iniitation, elongation, termination, other

Systematic ID	Gene name	Product description	Budding yeast orthologs	Human orthologs
SPBC28E12.04	cbp7	cytochrome b translation regulator Cbp7	CBS2
SPAC22H10.09	cbp8	cytochrome b translation regulator Cbp8
SPAC1420.04c	cox1101	cytochrome c oxidase assembly protein Cox1101/ mitochondrial ribosome assembly protein Rsm22 fusion protein	COX11,RSM22	COX11,METTL17
SPAC19B12.13	cox1102	cytochrome c oxidase assembly protein Cox1102/ mitochondrial ribosome assembly protein Rsm2202, fusion protein	COX11,RSM22	COX11,METTL17
SPAC19A8.14	pth2	mitochondrial aminoacyl-tRNA hydrolase Pth2	PTH2	PTRH2
SPBC1105.18c	pth3	mitochondrial aminoacyl-tRNA hydrolase Pth3	RSO55	MTRFR
SPAC8C9.06c	ppr4	mitochondrial Cox1 translation regulator Ppr4	PET309
SPBC8D2.12c	tac1	mitochondrial Cox1 translational activator Tac1	DPC29	TACO1
SPBC11C11.11c	irc3	mitochondrial DNA branch migration helicase Irc3	IRC3
SPAC1B3.04c	guf1	mitochondrial elongation factor GTPase Guf1	GUF1	GUF1
SPBC30B4.06c	ips1	mitochondrial GIDA family tRNA uridine 5-carboxymethylaminomethyl modification enzyme Ips1	MTO1	MTO1
SPBC646.03	gta1	mitochondrial glutamyl-tRNA amidotransferase alpha subunit Gta1	HER2	QRSL1
SPAC343.13	gta2	mitochondrial glutamyl-tRNA amidotransferase beta subunit Gta2	PET112	GATB
SPCC777.11	gta3	mitochondrial glutamyl-tRNA amidotransferase complex subunit Gta3	GTF1	GATC
SPAC23C11.17	mdm38	mitochondrial inner membrane protein involved in translation Mdm38	MDM38,YLH47	LETM1,LETM2
SPAC1805.09c	fmt1	mitochondrial methionyl-tRNA formyltransferase Fmt1	FMT1	MTFMT
SPAC29B12.05c	mtq1	mitochondrial N(5)-glutamine methyltransferase	MTQ1	HEMK1
SPBC2D10.15c	pth1	mitochondrial peptidyl-tRNA hydrolase Pth1	PTH1	PTRH1
SPBC106.19	ppr10	mitochondrial PPR repeat protein Ppr10
SPBC800.07c	tsf1	mitochondrial translation elongation factor EF-Ts Tsf1		TSFM
SPBC9B6.04c	tuf1	mitochondrial translation elongation factor EF-Tu Tuf1	TUF1	TUFM
SPBC1306.01c	mef1	mitochondrial translation elongation factor G Mef1	MEF1	GFM1
SPBC660.10	mef2	mitochondrial translation elongation factor G Mef2	MEF2	GFM2
SPBC25B2.04c	mtg1	mitochondrial translation factor (GTPase) Mtg1	MTG1	MTG1
SPAP8A3.11c	mtg2	mitochondrial translation factor (GTPase) Mtg2	MTG2	GTPBP10
SPAC5D6.12	mtf2	mitochondrial translation factor Mtf2	MTF2
SPAP8A3.14c	sls1	mitochondrial translation factor Sls1	SLS1
SPBC1271.15c	mti2	mitochondrial translation initiation factor IF-2Mt/Mti2	IFM1	MTIF2
SPBC18E5.13	mti3	mitochondrial translation initiation factor Mti3	AIM23	MTIF3
SPAC2F7.17	mrf1	mitochondrial translation release factor	MRF1	MTRF1,MTRF1L
SPBC1709.09	rrf1	mitochondrial translation termination factor Rrf1	RRF1	MRRF
SPAPB1E7.11c	mpa1	mitochondrial translational activator, Mpa1
SPAC222.05c	mss1	mitochondrial tRNA wobble uridine modification GTPase Mss1	MSS1	GTPBP3
SPAC12B10.08c	til1	mitochondrial tRNA(Ile)-lysidine synthetase Til1

[ValWood]

I started a model
http://noctua.geneontology.org/workbench/noctua-visual-pathway-editor/?model_id=gomodel%3A67086be200000519

Tasks

• re-read nathalies review
• is https://www.pombase.org/gene/SPBC3H7.04 a bona fida mitochondrial subunit
• annotate the outstanding papers (list...)
• Need to find which tRNA is the initiator methionine
• GO translation factor issues reported. Need to reannotate when resolved
  translation factors, various geneontology/go-ontology#29089
• It isn't clear how to model the output of a process in GO-CAM (i.e. to have the proteins encoded in the mitochondrial genome as outputs of mitochondria translation) In this case, modelling the output of a complex like mitochondrial translation initiation complex (does not exist) might work (could add as a child of GO:0070992 translation initiation complex)
• Add mitoribosome small and large subunits once Complex IDs filter through
• mef2 doesn't appear to be an elongation factor it's a recycling factor, now reannotated and renamed to GFM2 to remove confusion (need to notify SGD, and check no PAINT annotations)
• mtg1 SGD annotates to translation https://www.yeastgenome.org/reference/S000073563 but the authors speculate this is ribosome assembly
• MtIF3 promotes subunit dissociation and prevents premature reassociation of the large subunit. check.
• upstream "regulators" are these part of translation or regulating translation (i.e. ppr10 and mpa1 which recruit tifs to the ribosome). The author of ppr10 says it likely functions preinitiation.
• waiting for https://www.pombase.org/reference/PMID:38499152 - has more translation factors. mrh5 needs to be added to above list
• check Nathalies paper, this is probably not a bona fida ribosomal subunit SPBC3H7.04

[sjm41]

I think we addressed most of the fly mito translation factor issues in this paper:
https://www.tandfonline.com/doi/full/10.1080/19336934.2016.1220464
(Of course, there might be new issues by now....)

[ValWood]

I think we addressed most of the fly mito translation factor issues in this paper:

that's handy.

We have this for pombe https://iubmb.onlinelibrary.wiley.com/doi/10.1002/iub.2801
figure 3 is fairly up-to-date

Then there are the "upstream" regulators, figure 4 (Mainly PPR repeat proteins). I am not sure what the activities of these should be. The authors call them 'translation activators' but I'm not sure if they are activators in the GO sense, and would need to be able to supply their specific RNA inputs

[ValWood]

• asked SGD to migrate ppr4 from translation regulator to translation activator (update ISO and ask to be PAINTED)

[ValWood]

The mitochondrial mRNAs have mRNA specific activators. UNfortunately these don't appear to be conserved between species (the gene products are conserved but he targets appear to be different, which is odd.
I will begin to summarize here:

GENERAL TRANSLATION FACTORS

description	Gene pombe	role pombe	gene S. cerevisiae	role S. cerevisiae	gene human	role human
general translation factor	sls1	??	SLS1	GTF (all transcripts)	??	??
general translation factor (PPR repeat)	mtf2	??	MTF2	GTF (all transcripts)	??	??
PPR domain	ppr2	GTF	??	???	??	??
PPR domain	ppr10	GTF(protein RNA adaptor, especially cob1 and cox10, AND adaptor between initiation factors and ribosome)	??	???	??	??
general translation activator	mpa1	GTF(binds ppr10)	??	???	??	??
PPR domain	???	???)	??	???	LRPPRC	GTF
general translation activator	???	???)	??	???	IGF2BP1	GTF
general translation activator	???	???)	??	???	DHX30	GTF

FACTORS SPECIFICALLY AFFECTING COX1 TRANSLATION IN ANY SPECIES (from xxx intro)

description	Gene pombe	role pombe	gene S. cerevisiae	role S. cerevisiae	gene human	role human
?	mss51	NOT cox1 translation	MSS51	cox1 translation (couples cox1 translation & complex IV ass.)	MSS51	?
?	mam33	?	MAM33	cox1 translation	C1QBP (check looks odd)	?
RNA helicase	mss116	?	MSS116	cox1 translation (unwinds cox1 mRNA)	?	?
PPR repeat protein	ppr4	cox1 translation (Mrh5C complex)	PET309	cox1 translation (binds cox1 5' UTR, recruits Mss116)	?	?
RNA helicase	mrh5	cox1 translation (Mrh5C complex)	?	?	?	?
translation factor	sls1	cox1 translation (Mrh5C complex)	SLS1	translation factor	?	?
?	mtf2	cox1 translation (Mrh5C complex)	MTF2	transcription-> translation coupling factor	?	?
translation factor	tac1	translation role inferred	DPC29	general translation factor	TACO1	cox1 translation (translation activator)
--	--	--	--	--	MITRAC (unclear which gene this is)	cox1 translation
cytochrome C assembly protein	cox14	assembly role inferred from SGD	COX14	cyc c assembly and -ve reg of cox1 translation?	COX14(C12orf62)	cox1 translation

[ValWood]

Add this later:
Translation of complex III subunit Cob1 (also called COB or Cytb) involves Cbp1, required for cob1 mRNA stability, Cbs1 and Cbs2, which bind cob1 50-UTR and mitoribosome, and the Cbp3-Cbp6 complex, which like Mss51, coordinates cob1 mRNA translation and the subse- quent assembly of complex III (10). The Cbp3-Cbp6 complex activates Cob1 translation by displacing Cbs1 from the mitoribosome exit tunnel and supports hemylation of newly synthesized Cob1 (10). More importantly, this complex par- ticipates in feedback regulation of Cob1 translation by disso- ciating from nascent Cob1 upon Qcr8 association and recycling back to the mitoribosome for use in further rounds of Cob1 translation (11

[ValWood]

It seems that mrh5 is the functional ortholog of S. cerevisiae mss116 but S. pombe mss116 has a clearer ortholog).
mss116 It is the best structural hit of mrh5 in pdb so they may be paralogs.
It is possible that orthology tools are confused by the slightly extended N-term on pombe mrh5 ( this should probably be trimmed by 19 aa to the next methionine which would give it a mitochondrial transit peptide.

[ValWood]

Noctua modelling questions

1. How should I curate gene products, which are part of translation, but instead upstream of initiation?
   Historically I used "positive regulation of translation" because that's what the authors used.
   This doesn't seem quite right, but not sure how else to do it.
   I'll put this on the list for Noctua call

2. Also how to model the output of a process

3. Using gene names as inputs will be misleading for recruiting transcripts to the translation machinery because we will be using the same ID for the input (mRNA ) and output (protein)

[hattrill]

Ah! I see - my gut feeling is that if they don't belong to another 'process' and are needed for translation, then they are part of translation and prob need to widen the defintion - but would be good to see how this models and see a workable solution.

[ValWood]

Agree; these are definitely 'part of' translation. They are doing tasks like acting as adaptors between the TIFss and the SSU, or even adaptors for the mRNAs, so they are pretty central to the process!