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The ~ 1.5 Moz Yaouré gold deposit, which is located within the Birimian greenstone belts of central Côte d’Ivoire (West Africa), is associated with two stages of economic gold mineralization. Both ore-forming stages occurred during protracted E-W-directed shortening associated with the Eburnean orogeny. The first mineralization stage is hosted by fault-fill veins along conjugate ENE-striking (dextral) and WNW-striking (sinistral) strike-slip fault arrays. This ore stage is associated with a polymetallic assemblage including Mo, Bi, Pb, W, Te, Ag, and Au and cryptic alteration in wall rocks. The second and main gold mineralization stage is associated with a low-displacement fault-fracture-vein mesh formed during a reverse faulting episode. This second gold phase is associated with a polymetallic assemblage including W and Au ± Pb and is characterized by pronounced albite-ankerite-pyrite hydrothermal alteration in wall rocks. Shear veins associated with this second mineralization episode formed during episodic fluid pressure variations under low differential stress within pre-existing low-angle reverse fault planes. Permeability destruction by albite-ankerite-pyrite hydrothermal sealing of these low-angle reverse faults resulted in fluid pressure build-up and ultimately in the development of extension veins under low differential stress in the late stages of the structural evolution of the deposit. This study presents the structural evolution of a polyphase orogenic gold deposit and highlights that the interplay between fault zone activity, hydrothermal alteration, and fluid pressure fluctuations at low differential and deviatoric stresses were key in controlling fluid flow and the formation of ore within optimally-oriented faults.

The southern part of the West African Craton includes the Baoulé-Mossi Domain, the world’s premier Paleoproterozoic gold province (~10,000 metric ton gold endowment). Structural, metamorphic, and geochronological data suggest gold mineralisation occurred during three episodes that span much of the Eoeburnean and Eburnean orogenic cycles. Eoeburnean orogenic and rare skarn-hosted gold deposits formed between ca. 2200 and 2135 Ma during repeated episodes of volcanism, plutonism, and shortening, which thickened the Paleoproterozoic crust. Early Eburnean orogenic and placer gold deposits formed between ca. 2110 and 2095 Ma during inversion, metamorphism, and subsequent oblique shortening of intra-orogenic basins filled after ca. 2135 Ma. This episode of mineralisation terminated when the Baoulé-Mossi Domain docked with the Archean Kénéma-Man Domain at ca. 2095 Ma. Late Eburnean orogenic and less common intrusion-related gold deposits formed between ca. 2095 and 2060 Ma during strike-slip to oblique-slip tectonics, post-collisional high-K plutonism and crustal reworking across the western and southern Baoulé-Mossi Domain. Eoeburnean gold deposits include ca. 10 % of the gold endowment of the Baoulé-Mossi Domain, whereas the Early Eburnean and Late Eburnean deposits include ca. 50–70% and 20–40%, respectively. Here, we highlight the favourable confluence of accretion-collision tectonics, involving juvenile crust formation as well as protracted magmatic, metamorphic, and deformation histories that resulted in diachronous gold events spread over at least 100 myr throughout the Baoulé-Mossi Domain.

The Bonikro gold deposit and satellite Hiré open pits are located at the southern tip of the Oumé-Féttékro granite–greenstone belt in Côte d’Ivoire. Country rocks in the region have undergone polyphase deformation and prolonged arc magmatism during the Paleoproterozoic Eburnean orogeny. Intrusive host rocks at Hiré and Bonikro have been dated at 2180 ± 6 and 2086 ± 4 Ma (U–Pb on zircon), respectively. These plutonic bodies acted as favourable sites for fluid flow due to their brittle rheological characteristics. Gold mineralisation at Bonikro is hosted by (i) a sheeted quartz vein array characterised by an Au–W–Bi–Te–Ag metal association, in the cupola of a porphyritic granodiorite; and (ii) an overprinting swarm of fault-fill smoky quartz–(molybdenite) veins. Gold mineralisation at Hiré is shear-hosted and shares a similar relative timing with the latter set of auriferous veins. This second phase of gold mineralisation occurred during a period of transcurrent tectonics late in the Eburnean tectono-magmatic history, soon after the cessation of compressional deformation. It is responsible for the bulk of gold resources in the region (e.g. Bonikro, Hiré, Agbahou) and has been dated at 2074 ± 16 Ma (Re–Os on molybdenite). The integration of structural–paragenetic relationships with high precision dating of magmatic and hydrothermal events highlights the superposition of late Eburnean orogenic gold mineralisation on an earlier intrusion-related gold system linked to the local emplacement of a porphyritic granodiorite at Bonikro and illustrates the genetic diversity of Paleoproterozoic granitoid-hosted gold mineralisation in the West African Craton. It also further supports that gold mineralisations in the West African Craton occurred diachronously throughout the Eburnean orogeny through a variety of deposit types including Au-skarn, intrusion-related Au, orogenic Au, and porphyry Cu–Au.

High-grade (> 10 g/t) gold mineralization in orogenic gold deposits is of significant economic importance. Understanding the formation of such enriched ore zones is critical for gold exploration success. The world-class Jundee-Bogada gold camp in the Yilgarn Craton of Western Australia comprises both high-grade (avg. > 10 g/t, Jundee deposit) and low-grade (avg. < 3 g/t, Bogada prospect) lodes, despite shared host stratigraphy. The paragenetic framework established for the Jundee gold deposit suggests that the overall gold endowment developed over three deformation events. An early episode of low-grade gold mineralization is associated with colloform-crustiform veins that formed during extensional deformation (DJB2A). A switch to transtensional deformation (DJB2B) resulted in brecciation of the colloform-crustiform veins and coeval deposition of native gold. Late reverse faults record evidence for a third mineralization stage resulting from a NE-SW-directed shortening (DJB3). Mineralization during this late stage was dominantly low-grade, with local occurrences of ultra-high-grade ore zones (> 100 g/t). Each event records transient changes in fluid chemistry during continued hydrothermal activity that spanned local deformation histories. We argue that at the Jundee gold deposit, protracted gold enrichment during three polyphased mineralization episodes resulted in the formation of high-grade gold ores. Whereas the complete metallogenic history is recorded at the Jundee deposit, gold within the Bogada prospect was introduced solely during the late contractional stage (DJB3), resulting in a bulk low-grade endowment. We hypothesize that gold enrichment in high-grade orogenic gold deposits is a direct consequence of the spatial superimposition of protracted ore-forming events.

Assimilation and prolonged suspension of crust-derived sulfide liquid in komatiites are essential to form Ni-rich mineralisation. Evaluating the spatial relationship between komatiite-hosted Ni mineralisation and crustal S sources may thus provide insights into mechanisms of transport, metal enrichment and deposition of assimilated sulfide liquid. This study applied facies analysis and S isotopes to sulfides in Ni-mineralised komatiites and stratigraphically underlying bimodal volcanic-volcaniclastic and sedimentary rocks, which formed during rifting in the Agnew-Wiluna Greenstone Belt, Western Australia. The results revealed a lateral variation from rift-distal sedimentary sulfides, through sulfidic BIF, to rift-proximal VMS-style sulfides, the latter of which was predominantly assimilated by komatiites. Both crustal and komatiite-hosted sulfides were overprinted by granite-related skarn alteration during later basin inversion. Spatial S isotopes correlation revealed that Ni mineralisation in komatiites predominantly formed < 5 km from their crustal S sources, excluding long lateral transport as the main metal enrichment mechanism. Rather, metal enrichment likely happened through multiple cycles of sulfide entrapment and entrainment in lava flow vortices that formed in the wake of topographic steps represented by syn-rift faults. These faults were the main loci for pre-existing crustal weaknesses, hydrothermal fluid circulation, and VMS-style sulfide deposition, which were subsequently utilised by komatiites for enhanced thermo-mechanical erosion and crustal sulfide assimilation. This study shows that proximity to the syn-rift faults was the dominant control on the formation of komatiite-hosted Ni–sulfide mineralisation, regardless of substrate lithology. The S isotope signatures of crustal sulfides may be used as a proxy to identify syn-rift faults in highly deformed terranes.

The > 9 Moz total aggregate gold endowment at the Edikan mine, Kumasi Basin, Ghana, is contained within a cluster of orogenic gold deposits located along the Akropong fault zone. The granitoid-hosted orebodies at Edikan (e.g., AG2, AG3, Fobinso, Esuajah), essentially an interconnected mesh of gold-bearing quartz veins, formed during deformation event D3Edk, which postdates the penetrative regional D2Edk deformation. The gold-bearing quartz veins developed in, and adjacent to, N-S- and NW-SE-trending, low-angle thrust faults that crosscut lithological contacts and earlier formed, steeply dipping D2Edk faults. Our paleostress analysis shows that the D3Edk deformation, during which the mineralized fault system developed, was characterized by a WNW-ESE “hybrid” compression that evolved to a strike-slip regime. This progressive deformation is best described with the following stress regimes: WNW-ESE transpression-pure compression (T1) associated with low-angle thrusting, subsequent transpression-strike-slip (T2), and later strike-slip-transtension (T3) associated with steeply dipping strike-slip faulting. The bulk of the granitoid-hosted gold mineralization at Edikan is associated with two principal sets of gold-bearing quartz veins, including low-angle fault-fill veins controlled by thrusts and shallow dipping oblique-extension veins that developed during T1. The activation of the reverse and sinistral strike-slip faults led to the development of restraining jogs characterized by abundant shallow and steeply dipping gold-quartz veins with moderately NE-plunging ore shoots. The geometry of the mineralized fault-fracture meshes is consistent with fault-valve behavior in a horizontal compressive stress regime under sustained conditions of supralithostatic fluid pressures at low differential stress.

Background Many transcript isoforms generated by intronic polyadenylation (IPA) encode isoforms of canonical proteins. Microproteins are an emerging class of small proteins translated from small open reading frames (sORFs) in noncoding RNAs and mRNAs, but their production by IPA isoforms is unknown. Results Here, by crossing 3′-seq, Ribo-Seq, and mass-spectrometry data, we identify 297 genes with a microprotein-coding IPA isoform terminating in a 5′UTR intron (coined miP-5′UTR-IPA isoform). By 3′-seq and long-read RNA-seq analyses in lung cancer cells treated with cisplatin, a DNA-cross-linking anticancer drug, we find that cisplatin globally favors the expression of (miP-5′UTR-)IPA isoforms relative to full-length mRNAs, mainly by decreasing the latter through an inhibition of transcription processivity in a FANCD2 and senataxin-dependent manner. The cisplatin-regulated miP-5′UTR-IPA isoform in the PRKAR1B gene is translated, as it is associated with light polysome fractions and contains Ribo-Seq-supported sORFs in its alternative last exon, and the microprotein (PRKAR1B-IPA-miP2) encoded by its sORF#2 is detected by Western blot and immunofluorescence. CRISPR editing of either the IPA site or the sORF#2 initiation site leads to decreased cell growth inhibition by cisplatin and camptothecin, another genotoxic drug. Mechanistically, PRKAR1B-IPA-miP2 promotes p53 protein induction by cisplatin. Finally, 70 miP-5′UTR-IPA isoforms are detected in normal cells, and 143 are upregulated by cisplatin. Conclusions Here, we show that IPA isoforms are a novel source of microproteins, and we reveal the novel paradigm of miP-5′UTR-IPA genes that produce both a canonical full-length mRNA and a microprotein-coding IPA isoform.

ADP ribosylation factor guanine nucleotide exchange factors (ARFGEFs) are a family of proteins implicated in cellular trafficking between the Golgi apparatus and the plasma membrane through vesicle formation. Among them is ARFGEF1/BIG1, a protein involved in axon elongation, neurite development, and polarization processes. ARFGEF1 has been previously suggested as a candidate gene for different types of epilepsies, although its implication in human disease has not been well characterized. International data sharing, in silico predictions, and in vitro assays with minigene study, western blot analyses, and RNA sequencing. We identified 13 individuals with heterozygous likely pathogenic variants in ARFGEF1. These individuals displayed congruent clinical features of developmental delay, behavioral problems, abnormal findings on brain magnetic resonance image (MRI), and epilepsy for almost half of them. While nearly half of the cohort carried de novo variants, at least 40% of variants were inherited from mildly affected parents who were clinically re-evaluated by reverse phenotyping. Our in silico predictions and in vitro assays support the contention that ARFGEF1-related conditions are caused by haploinsufficiency, and are transmitted in an autosomal dominant fashion with variable expressivity. We provide evidence that loss-of-function variants in ARFGEF1 are implicated in sporadic and familial cases of developmental delay with or without epilepsy.

Transcript isoforms generated by intronic polyadenylation (IPA) are widely regulated in various biological processes and often encode protein isoforms. Microproteins are small proteins translated from small open reading frames (sORFs) in noncoding RNAs and mRNAs, but their production by IPA isoforms is unknown. Using 3'-seq and long-read RNA-seq analyses in lung cancer cells, we show that cisplatin, a DNA-crosslinking anticancer agent, upregulates IPA isoforms relative to full-length mRNAs in long genes. A subset of cisplatin-regulated IPA isoforms are poorly associated with heavy polysomes and terminate upstream of the annotated translation initiation codon of genes. Such IPA isoforms in the PHF20 and PRKAR1B genes are associated with light polysomes, contain Ribo-Seq-supported sORFs in an alternative last exon within the annotated 5'UTR part of genes, and are translated into microproteins. For PRKAR1B, the microprotein was detected by Western blot and immunofluorescence after transfection of a tagged isoform; and siRNA depletion of the endogenous IPA isoform, CRISPR deletion of the IPA site, or CRISPR mutation of the sORF initiation codon led to increased cell survival to cisplatin. Based on Ribo-Seq and mass-spectrometry data sets, we identified 156 genes producing both a canonical protein-coding mRNA and a microprotein-coding 5'UTR-located IPA isoform (coined miP-5'UTR-IPA isoform) regulated by cisplatin. Finally, the regulation of (miP-5'UTR-)IPA versus full-length isoforms by cisplatin involved an inhibition of transcription processivity in a FANCD2 and senataxin-dependent manner. Altogether, these findings reveal the novel paradigm of miP-5'UTR-IPA genes and their role in cancer cell response to a genotoxic agent.Competing Interest StatementS. Vagner is a scientific cofounder of Ribonexus.Footnotes* https://github.com/InstitutCurie/3-SMART* https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE119978* https://genome.ucsc.edu/s/clabbe/visuCDDPpaper_Dutertre2021