Minor intron splicing is regulated by FUS and affected by ALS-associated FUS mutants

Fused in sarcoma (FUS) is a ubiquitously expressed RNA-binding protein proposed to function in various RNA metabolic pathways, including transcription regulation, pre-mRNA splicing, RNA transport and microRNA processing. Mutations in the FUS gene were identified in patients with amyotrophic lateral sclerosis (ALS), but the pathomechanisms by which these mutations cause ALS are not known. Here, we show that FUS interacts with the minor spliceosome constituent U11 snRNP, binds preferentially to minor introns and directly regulates their removal. Furthermore, a FUS knockout in neuroblastoma cells strongly disturbs the splicing of minor intron-containing mRNAs, among them mRNAs required for action potential transmission and for functional spinal motor units. Moreover, an ALS-associated FUS mutant that forms cytoplasmic aggregates inhibits splicing of minor introns by trapping U11 and U12 snRNAs in these aggregates. Collectively, our findings suggest a possible pathomechanism for ALS in which mutated FUS inhibits correct splicing of minor introns in mRNAs encoding proteins required for motor neuron survival.

(Table S1, S4) Campanian-Maastrichtian benthic foraminifera from ODP Hole 113-690C

During the latest Cretaceous cooling phase, a positive shift in benthic foraminiferal d18O values lasting about 1.5 Myr (71.5-70 Ma) can be observed at a global scale (Campanian-Maastrichtian Boundary Event, CMBE). This d18O excursion is interpreted as being influenced by a change in intermediate- to deep-water circulation or by temporal build-up of Antarctic ice sheets. Here we test whether benthic foraminiferal assemblages from a southern high-latitudinal site near Antarctica (ODP Site 690) are influenced by the CMBE. If the d18O transition reflects a change in intermediate- to deep-water circulation from low-latitude to high-latitude water masses, then this change would result in cooler temperatures, higher oxygen concentration, and possibly lower organic-matter flux at the seafloor, resulting in a major benthic foraminiferal assemblage change. If, however, the d18O transition was mainly triggered by ice formation, no considerable compositional difference in benthic foraminiferal assemblages would be expected. Our data show a separation of the studied succession into two parts with distinctly different benthic foraminiferal assemblages. Species dominating the older part (73.0-70.5 Ma) tolerate less bottom water oxygenation and are typical components of low-latitude assemblages. In contrast, the younger part (70.0-68.0 Ma) is characterized by species that indicate well-oxygenated bottom waters and species common in high-latitude assemblages. We interpret the observed change in benthic foraminiferal assemblages toward a well-oxygenated environment to reflect the onset of a shift from low-latitude toward high-latitude dominated intermediate- to deep-water sources. This implies that a change in oceanic circulation was at least a major component of the CMBE.

Report of progress - Geological Survey of Canada.

Contents of each report may be found in "List of publications of the Geological survey of Canada. 1906."

Greek writers of Roman history : some reflections upon the authorities used by Plutarch and Appianus /

The fons primarius of Plutarch's life of Fabius Maximus. -- The common Greek sources of Plutarch and Appianus for Roman history. -- King Juba's Historia romana.

History of the war in the Peninsula and in the south of France, from the year 1807 to the year 1814,

Mode of access: Internet.

Johann Samuel Traugott Gehler's Physikalisches Wörterbuch,

Vol. 11: Neu bearb. von Brandes, Gmelin, Horner, Littrow, Muncke, Pfaff ... Sach- und namen-register mit ergänzenden zusätzen von G. W. Muncke ... Nebst nachträgen zum Verzeichniss geographischer ortsbestimmungen von C. L. v. Littrow.

Life of General Sir William Napier /

Mode of access: Internet.

Zur Beurtheilung Napoleon's und seiner neusten Tadler und Lobredner : besonders in Beziehung auf die Zeit von 1810-1813 /

"Aus dem Archiv f��r Geschichte und Literatur von Fr. Chr. Schlosser und G. A. Bercht."

History of the war in the Peninsula, and in the south of France, from the year 1807 to the year 1814.

v.1: 4th ed., 1848; v.2: 3d ed., 1838; v.3: 3d ed., 1840; v.4: 2d ed., 1846; v.5: 1836; v.6: 1840.

Fifteen selected studies for the piano, op. 20 /

Mode of access: Internet.

Philodem von der Musik : ein Auszug aus dessen viertem Buche /

Includes bibliographical references.

Dissertatio anatomico-physiologica de omento, quam annuente ... Facultate medica Lipsiensi sub praesidio Dn. Augusti Quirini Rivini ... placidae philiatrorum ventilationi exponit ad diem XXVII. augusti anno 1717 ... /

Mode of access: Internet.

Vaterländisches Museum.

Kirchner, J. Bibliographie der Zeitschriften des deutschen Sprachgebietes bis 1900

Erinnerungen an Graf Stefan Szécsenyi.

Mode of access: Internet.

Religionsphilosophie /

Includes bibliographical references.