34 research outputs found
Modulation of translational decoding by m6A modification of mRNA
Get PDFN 6 -methyladenosine (m 6 A) is an abundant, dynamic mRNA modification that regulates key steps of cellular mRNA metabolism. m 6 A in the mRNA coding regions inhibits translation elongation. Here, we show how m 6 A modulates decoding in the bacterial translation system using a combination of rapid kinetics, smFRET and single-particle cryo-EM. We show that, while the modification does not impair the initial binding of aminoacyl-tRNA to the ribosome, in the presence of m 6 A fewer ribosomes complete the decoding process due to the lower stability of the complexes and enhanced tRNA drop-off. The mRNA codon adopts a π-stacked codon conformation that is remodeled upon aminoacyl-tRNA binding. m 6 A does not exclude canonical codon-anticodon geometry, but favors alternative more dynamic conformations that are rejected by the ribosome. These results highlight how modifications outside the Watson-Crick edge can still interfere with codon-anticodon base pairing and complex recognition by the ribosome, thereby modulating the translational efficiency of modified mRNAs
Structural and Functional Characterization of the Conserved Nup82 Subcomplex Located on the Cytoplasmic Side of the Yeast Nuclear Pore Complex
No full textNuclear pore complexes (NPCs) are huge, proteinaceous assemblies, embedded in the nuclear envelope that act as gateways between the cytoplasm and nucleoplasm. A single NPC is formed from ~30 different nucleoporins, present in multiple copies. The vast majority of nucleoporins is organized in distinct subcomplexes. A number of NPC modules have been described in the past, but the structure of the tetrameric Nup82-Nup159C-Nsp1C-Dyn2 complex, located at the cytoplasmic side of the NPC and involved in nuclear mRNA export, remained elusive.
My PhD study has focused on the conserved C-domain of Nup159, the key subunit of the Nup82 complex. Nup159-C harbors an essential -helical subdomain (H1), which is able to homo-dimerize through a coiled-coil interaction. Mutation in this region disturbs homo-dimerization and Nup82 complex assembly. The linker sequence prior to the essential H1 sub-domain turned out to be critical for dynein light chain (Dyn2) recruitment at the DIDNup159 motif (dynein light chain interacting domain), which binds five Dyn2 dimers. This finding suggests that DIDNup159 and H1 domains require a certain distance for Dyn2 binding to ensure the efficient Nup82 complex assembly and incorporation into the NPC scaffold. To gain more insight into the structure of the Nup82 complex, I have applied a method to reconstitute in vivo and subsequently isolate the essential structural core of the Nup82 module devoid of flexible FG repeats. Biochemical, biophysical and electron microscopy analysis unraveled that the Nup82 complex consists of a 20 nm stalk formed by the DIDNup159-Dyn2 and an asymmetric ’head’ structure that contains four Nup82 molecules with different properties and the helical C-domains of Nup159 and Nsp1, leading to a large assembly with a molecular mass in the megadalton range. Furthermore, cross-linking mass spectrometry allowed to map the interaction regions between four subunits of the complex.
In conclusion, the study revealed for the first time the three dimensional (3D) architecture of the Nup82-Nup159C-Nsp1C-Dyn2 complex with Nup159 C-domain forming the key self-dimerizing scaffold
Using financial analysis to evaluate company's financial health - case of Telekomunikacja Polska S.A.
No full textpraca magistersk
La polisemia y la sinonimia en el lenguaje jurídico. Estudio comparativo español-polaco
Get PDFCasi todos los idiomas se
caracterizan por la presencia de la sinonimia y la polisem
ia
que, a
parte de ser una muestra de la riqueza lingüística del lenguaje en general, son
las figuras muy vinculadas con los lenguajes de especialidad. El lenguaje
jurídico
que
nos ocupará en el pres
ente estudio, lejos de ser un
í
voco como muy a menudo se le
atribuye, se caracteriza por la elevada presencia de ambos fenómenos. El objeto
principal del nuestro trabajo es dar una prueba a esta afirmación a través de un
análisis de los términos propios tan
to para el lenguaje general como para el lenguaje
jurídicoAlmost every language sufers from a presence of a s
ynonymy and polysemy which
are, besides of being a sign o
f the lexical richness of language in general, are also the
linguistic figures linked to specialized languages. The legal language that will interest
us in this paper stays far away from transmitting the univocity that is usually
attributed to it and it is
characterized by more than a representative presence of both
phenomena. In the present study we aim to prove this statement through the analysis
of some terms proper for both general and legal language
Tax inspections as a response of the tax collection institutions to turnover tax evasion. Case study of X
No full textpraca magistersk
Research in the clinical setting : a qualitative study of the value of play research in the continuing education of occupational therapists.
No full textOccupational therapists have always recognized playas an important part
of a child's life. However, until recently play has been viewed as a medium for
reaching treatment goals, rather than as an activity that is valuable in and of itself.
If occupational therapists think of playas the primary activity or occupation of
childhood, then play should be a very important area of focus for paediatric
clinicians.
In order to assist children to become as independent as possible with play
and to have fulfilling play experiences the occupational therapist needs to have a
clear understanding of how to assess, set goals which lead towards competence in
play, and promote play. Recent play literature has placed importance on play
behaviours and looking at the relationship between the child and both the human
and nonhuman environment. Believing that play and playfulness can and should be
promoted, for children with physical disabilities, requires that therapists learn new
assessment and intervention strategies.
A new assessment tool, The Test of Playfulness, was developed by Bundy
in 1994. It addressed play behaviours and environmental influences. The author,
a co-investigator and eight occupational therapists were involved in a playfulness
study using this test to compare the playfulness of children with physical
disabilities with their able-bodied peers. After the study was completed the author
questioned whether or not involvement in the playfulness study was enough of a
change agent to bring about transformative learning in order to further the eight
occupational therapists' education about play
Characteristics of snow cover in urban and rural area based on data from Cracow and Gaik-Brzezowa
No full text
Promiscuity in post-transcriptional control of gene expression:<i>Drosophila</i>sex-lethal and its regulatory partnerships
Get PDFLA POLISEMIA Y LA SINONIMIA EN EL LENGUAJE JURÍDICO – ESTUDIO COMPARATIVO ESPAÑOL-POLACO
No full textCasi todos los idiomas se caracterizan por la presencia de la sinonimia y la polisemia que, aparte de ser una muestra de la riqueza lingüística del lenguaje en general, son las figuras muy vinculadas con los lenguajes de especialidad. El lenguaje jurídico que nos ocupará en el presente estudio, lejos de ser unívoco como muy a menudo se le atribuye, se caracteriza por la elevada presencia de ambos fenómenos. El objeto principal del nuestro trabajo es dar una prueba a esta afirmación a través de un análisis de los términos propios tanto para el lenguaje general como para el lenguaje jurídico
