Processing of Capped Intronless Pre-mRNA (Homo sapiens)

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1, 3, 8, 9, 117cytosolnucleoplasmZNF473 SNRPB CPSF2 CappedIntronlessHistonepre-mRNA:CBP80:CBP20:SLBPPAPOLA PCF11 CPSF3 FIP1L1 SLBP PCF11 Mature Intronless transcript derived Histone mRNA CPSF2 U7 snRNA SNRPD3 SNRPE CPSF4 NCBP2 CPSF1 upstreammRNAfragment:CPSF:PAP:PABPN1 complexCPSF3 CSTF2T CF I - 68 kDa subunit SNRPG SYMPK CPSFNCBP2 NCBP2 Mature Intronless transcript derived Histone mRNA CSTF1 SYMPK ZNF473 NCBP1 CSTF2T CSTF3 NCBP1 CSTF1 SNRPB SLBPPABPN1 Capped intronless pre-mRNA LSM10 WDR33 CF I - 68 kDa subunit NCBP2 CLP1 SLBP NUDT21 intronless pre-mRNAcleavage complexNCBP2 Capped intronless pre-mRNA CPSF2 CPSF7 NCBP2 CF IIIntronless Histone pre-mRNA CstFCPSF1 CLP1 CPSF1 NCBP1 Intronless Histone pre-mRNA Capped intronless pre-mRNA CSTF3 SYMPK Mature intronless transcript derived mRNA CappedIntronlessHistonepre-mRNA:CBP80:CBP20:SLBP:ZFP100 ComplexCPSF4 SNRPF CSTF2 SYMPK WDR33 SLBP CPSF2 CPSF3 PAPOLA Capped IntronlessHistonepre-mRNA:CBC:ZFP100ComplexCF ISNRPD3 CPSF3 CSTF2T Capped IntronlessHistonepre-mRNA:CBCcomplexNCBP2 NCBP1 SYMPK CSTF2 CPSF1 FIP1L1 CPSF4 SNRPE WDR33 CPSF3 FIP1L1 Intronless Histone pre-mRNA CPSF3 NCBP2 CSTF1 Mature intronlessderived mRNAcomplexSNRPB MatureIntronlesstranscriptderivedHistonemRNA:SLBP:CBP80:CBP20CstF:CPSF:cappedintronlesspre-mRNA:CBCcomplexCSTF3 Mature intronlesstranscript derivedHistonepre-mRNA:CBCcomplexNCBP1 FIP1L1 Capped intronless pre-mRNA SYMPK SNRPE PAPOLAZNF473 CPSF1 PABPN1WDR33 NCBP2 CPSF4 CF I - 72 kDa subunit NCBP1 NCBP1 U7 snRNA FIP1L1 downstreamintronless mRNAfragmentCPSF2 LSM11 NCBP1 Intronless Histone pre-mRNA U7 snRNP:ZNF473upstream intronless mRNA fragment CPSF2 NCBP1 SNRPD3 NCBP2 SNRPG CF I - 72 kDa subunit NCBP1 SNRPG CPSF7 WDR33 NUDT21 CSTF2 NCBP1 LSM11 NCBP1 LSM11 LSM10 U7 snRNA NCBP2 CPSF:cappedintronlesspre-mRNA:CBCcomplexSNRPF WDR33 capped intronlesspre-mRNA:CBCcomplexLSM10 CPSF1 FIP1L1 CPSF4 SNRPF PABPN1 CPSF4 NCBP2 2, 5, 610, 124


Description

Co-transcriptional pre-mRNA splicing is not obligatory. Pre-mRNA splicing begins co-transcriptionally and often continues post-transcriptionally. Human genes contain an average of nine introns per gene, which cannot serve as splicing substrates until both 5' and 3' ends of each intron are synthesized. Thus the time that it takes for pol II to synthesize each intron defines a minimal time and distance along the gene in which splicing factors can be recruited. The time that it takes for pol II to reach the end of the gene defines the maximal time in which splicing could occur co-transcriptionally. Thus, the kinetics of transcription can affect the kinetics of splicing.
There are two classes of intronless pre-mRNAs (mRNAs expressed from genes that lack introns). The first class encodes the replication dependent histone mRNAs. These mRNAs have unique 3' ends that do not have a polyA tail. The replication dependent histone mRNAs in all metazoans, as well as Chlamydomonas and Volvox fall into this class.

The second class of mRNAs end in polyA tails, which are formed by a mechanism similar to that which poly-adenylate pre-mRNAs containing introns. In the intronless genes there is a different method of replacing the 3' splice site that activates polyadenylation. View original pathway at:Reactome.</div>

Comments

Reactome-Converter 
Pathway is converted from Reactome ID: 75067
Reactome-version 
Reactome version: 66
Reactome Author 
Reactome Author: Marzluff, William F

Quality Tags

Ontology Terms

 

Bibliography

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  1. Sànchez R, Marzluff WF.; ''The stem-loop binding protein is required for efficient translation of histone mRNA in vivo and in vitro.''; PubMed Europe PMC
  2. Shi Y, Di Giammartino DC, Taylor D, Sarkeshik A, Rice WJ, Yates JR, Frank J, Manley JL.; ''Molecular architecture of the human pre-mRNA 3' processing complex.''; PubMed Europe PMC
  3. Gall JG.; ''Cajal bodies: the first 100 years.''; PubMed Europe PMC
  4. Dominski Z, Erkmann JA, Yang X, Sànchez R, Marzluff WF.; ''A novel zinc finger protein is associated with U7 snRNP and interacts with the stem-loop binding protein in the histone pre-mRNP to stimulate 3'-end processing.''; PubMed Europe PMC
  5. Kaufmann I, Martin G, Friedlein A, Langen H, Keller W.; ''Human Fip1 is a subunit of CPSF that binds to U-rich RNA elements and stimulates poly(A) polymerase.''; PubMed Europe PMC
  6. Schönemann L, Kühn U, Martin G, Schäfer P, Gruber AR, Keller W, Zavolan M, Wahle E.; ''Reconstitution of CPSF active in polyadenylation: recognition of the polyadenylation signal by WDR33.''; PubMed Europe PMC
  7. Martin F, Schaller A, Eglite S, Schümperli D, Müller B.; ''The gene for histone RNA hairpin binding protein is located on human chromosome 4 and encodes a novel type of RNA binding protein.''; PubMed Europe PMC
  8. Frey MR, Matera AG.; ''Coiled bodies contain U7 small nuclear RNA and associate with specific DNA sequences in interphase human cells.''; PubMed Europe PMC
  9. Marzluff WF, Gongidi P, Woods KR, Jin J, Maltais LJ.; ''The human and mouse replication-dependent histone genes.''; PubMed Europe PMC
  10. Yao C, Choi EA, Weng L, Xie X, Wan J, Xing Y, Moresco JJ, Tu PG, Yates JR, Shi Y.; ''Overlapping and distinct functions of CstF64 and CstF64τ in mammalian mRNA 3' processing.''; PubMed Europe PMC
  11. Dominski Z, Marzluff WF.; ''Formation of the 3' end of histone mRNA.''; PubMed Europe PMC
  12. Takagaki Y, Manley JL.; ''Complex protein interactions within the human polyadenylation machinery identify a novel component.''; PubMed Europe PMC

History

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CompareRevisionActionTimeUserComment
101239view11:13, 1 November 2018ReactomeTeamreactome version 66
100778view20:40, 31 October 2018ReactomeTeamreactome version 65
100321view19:17, 31 October 2018ReactomeTeamreactome version 64
99866view16:00, 31 October 2018ReactomeTeamreactome version 63
99423view14:36, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
99106view12:39, 31 October 2018ReactomeTeamreactome version 62
93946view13:46, 16 August 2017ReactomeTeamreactome version 61
93539view11:26, 9 August 2017ReactomeTeamreactome version 61
88116view10:07, 26 July 2016RyanmillerOntology Term : 'regulatory pathway' added !
86637view09:22, 11 July 2016ReactomeTeamreactome version 56
83073view09:53, 18 November 2015ReactomeTeamVersion54
81390view12:55, 21 August 2015ReactomeTeamVersion53
76858view08:13, 17 July 2014ReactomeTeamFixed remaining interactions
76563view11:54, 16 July 2014ReactomeTeamFixed remaining interactions
75896view09:55, 11 June 2014ReactomeTeamRe-fixing comment source
75596view10:44, 10 June 2014ReactomeTeamReactome 48 Update
74951view13:47, 8 May 2014AnweshaFixing comment source for displaying WikiPathways description
74595view08:38, 30 April 2014ReactomeTeamReactome46
42106view21:57, 4 March 2011MaintBotAutomatic update
39916view05:56, 21 January 2011MaintBotNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
CF I - 68 kDa subunit R-HSA-72013 (Reactome)
CF I - 72 kDa subunit R-HSA-72014 (Reactome)
CF IIComplexR-HSA-72020 (Reactome)
CF IComplexR-HSA-72015 (Reactome)
CLP1 ProteinQ92989 (Uniprot-TrEMBL)
CPSF1 ProteinQ10570 (Uniprot-TrEMBL)
CPSF2 ProteinQ9P2I0 (Uniprot-TrEMBL)
CPSF3 ProteinQ9UKF6 (Uniprot-TrEMBL)
CPSF4 ProteinO95639 (Uniprot-TrEMBL)
CPSF7 ProteinQ8N684 (Uniprot-TrEMBL)
CPSF:capped

intronless pre-mRNA:CBC

complex
ComplexR-HSA-112160 (Reactome)
CPSFComplexR-HSA-71995 (Reactome)
CSTF1 ProteinQ05048 (Uniprot-TrEMBL)
CSTF2 ProteinP33240 (Uniprot-TrEMBL)
CSTF2T ProteinQ9H0L4 (Uniprot-TrEMBL)
CSTF3 ProteinQ12996 (Uniprot-TrEMBL)
Capped

Intronless Histone

pre-mRNA:CBP80:CBP20:SLBP:ZFP100 Complex
ComplexR-HSA-110766 (Reactome)
Capped

Intronless Histone

pre-mRNA:CBP80:CBP20:SLBP
ComplexR-HSA-110759 (Reactome)
Capped Intronless

Histone pre-mRNA:CBC

complex
ComplexR-HSA-110758 (Reactome)
Capped Intronless

Histone pre-mRNA:CBC:ZFP100

Complex
ComplexR-HSA-112045 (Reactome)
Capped intronless pre-mRNA R-ALL-112158 (Reactome)
CstF:CPSF:capped

intronless pre-mRNA:CBC

complex
ComplexR-HSA-112161 (Reactome)
CstFComplexR-HSA-72006 (Reactome)
FIP1L1 ProteinQ6UN15 (Uniprot-TrEMBL)
Intronless Histone pre-mRNA R-ALL-110756 (Reactome)
LSM10 ProteinQ969L4 (Uniprot-TrEMBL)
LSM11 ProteinP83369 (Uniprot-TrEMBL)
Mature

Intronless transcript derived Histone

mRNA:SLBP:CBP80:CBP20
ComplexR-HSA-111682 (Reactome)
Mature Intronless transcript derived Histone mRNA R-ALL-111676 (Reactome)
Mature intronless

derived mRNA

complex
ComplexR-HSA-112167 (Reactome)
Mature intronless

transcript derived Histone pre-mRNA:CBC

complex
ComplexR-HSA-156959 (Reactome)
Mature intronless transcript derived mRNA R-ALL-158444 (Reactome) A mature mRNA that has been 3' cleaved, subsequently polyadenylated, and a m7G 5' cap. This product was derived from an intronless transcript.
NCBP1 ProteinQ09161 (Uniprot-TrEMBL)
NCBP2 ProteinP52298 (Uniprot-TrEMBL)
NUDT21 ProteinO43809 (Uniprot-TrEMBL)
PABPN1 ProteinQ86U42 (Uniprot-TrEMBL)
PABPN1ProteinQ86U42 (Uniprot-TrEMBL)
PAPOLA ProteinP51003 (Uniprot-TrEMBL)
PAPOLAProteinP51003 (Uniprot-TrEMBL)
PCF11 ProteinO94913 (Uniprot-TrEMBL)
SLBP ProteinQ14493 (Uniprot-TrEMBL)
SLBPProteinQ14493 (Uniprot-TrEMBL)
SNRPB ProteinP14678 (Uniprot-TrEMBL)
SNRPD3 ProteinP62318 (Uniprot-TrEMBL)
SNRPE ProteinP62304 (Uniprot-TrEMBL)
SNRPF ProteinP62306 (Uniprot-TrEMBL)
SNRPG ProteinP62308 (Uniprot-TrEMBL)
SYMPK ProteinQ92797 (Uniprot-TrEMBL)
U7 snRNA R-ALL-110761 (Reactome)
U7 snRNP:ZNF473ComplexR-HSA-110765 (Reactome)
WDR33 ProteinQ9C0J8 (Uniprot-TrEMBL)
ZNF473 ProteinQ8WTR7 (Uniprot-TrEMBL)
capped intronless

pre-mRNA:CBC

complex
ComplexR-HSA-112159 (Reactome)
downstream

intronless mRNA

fragment
R-ALL-112165 (Reactome)
intronless pre-mRNA cleavage complexComplexR-HSA-112162 (Reactome)
upstream

mRNA

fragment:CPSF:PAP:PABPN1 complex
ComplexR-HSA-112164 (Reactome)
upstream intronless mRNA fragment R-ALL-112163 (Reactome)

Annotated Interactions

View all...
SourceTargetTypeDatabase referenceComment
CF IArrowR-HSA-77592 (Reactome)
CF IArrowR-HSA-77593 (Reactome)
CF IIArrowR-HSA-77592 (Reactome)
CF IIArrowR-HSA-77593 (Reactome)
CF IIR-HSA-77591 (Reactome)
CF IR-HSA-77591 (Reactome)
CPSF:capped

intronless pre-mRNA:CBC

complex
ArrowR-HSA-77589 (Reactome)
CPSF:capped

intronless pre-mRNA:CBC

complex
R-HSA-77590 (Reactome)
CPSFR-HSA-77589 (Reactome)
Capped

Intronless Histone

pre-mRNA:CBP80:CBP20:SLBP:ZFP100 Complex
ArrowR-HSA-77585 (Reactome)
Capped

Intronless Histone

pre-mRNA:CBP80:CBP20:SLBP:ZFP100 Complex
R-HSA-77586 (Reactome)
Capped

Intronless Histone

pre-mRNA:CBP80:CBP20:SLBP
ArrowR-HSA-77584 (Reactome)
Capped

Intronless Histone

pre-mRNA:CBP80:CBP20:SLBP
R-HSA-77585 (Reactome)
Capped Intronless

Histone pre-mRNA:CBC

complex
R-HSA-111438 (Reactome)
Capped Intronless

Histone pre-mRNA:CBC

complex
R-HSA-77584 (Reactome)
Capped Intronless

Histone pre-mRNA:CBC:ZFP100

Complex
ArrowR-HSA-111438 (Reactome)
Capped Intronless

Histone pre-mRNA:CBC:ZFP100

Complex
R-HSA-111437 (Reactome)
CstF:CPSF:capped

intronless pre-mRNA:CBC

complex
ArrowR-HSA-77590 (Reactome)
CstF:CPSF:capped

intronless pre-mRNA:CBC

complex
R-HSA-77591 (Reactome)
CstFArrowR-HSA-77592 (Reactome)
CstFArrowR-HSA-77593 (Reactome)
CstFR-HSA-77590 (Reactome)
Mature

Intronless transcript derived Histone

mRNA:SLBP:CBP80:CBP20
ArrowR-HSA-77586 (Reactome)
Mature intronless

derived mRNA

complex
ArrowR-HSA-77593 (Reactome)
Mature intronless

transcript derived Histone pre-mRNA:CBC

complex
ArrowR-HSA-111437 (Reactome)
PABPN1ArrowR-HSA-77593 (Reactome)
PABPN1R-HSA-77591 (Reactome)
PAPOLAArrowR-HSA-77593 (Reactome)
PAPOLAR-HSA-77591 (Reactome)
R-HSA-111437 (Reactome) Processing is initiated once the U7 snRNP is loaded onto the pre-mRNA. The pre-mRNA HDE makes base-pairing contacts with the 5�² end of U7 snRNA. Binding of the U7 snRNP to the pre-mRNA is stabilized by interactions between a U7 snRNP protein, hZFP100 and other trans-acting factors, including the factor that catalyzes the cleavage reaction, which have yet to be defined. The cleavage occurs in the presence of EDTA as does the cleavage reaction in polyadenylation, it is likely that this reaction is catalyzed by a protein. There may well be additional proteins associated with the U7 snRNP, since the in vitro processing occurs in the absence of SLBP, it is possible that all the other factors required for processing are associated with the active form of the U7 snRNP.
R-HSA-111438 (Reactome) The U7 snRNP. This particle contains the U7 snRNA, the smallest of the snRNAs which varies from 57-70 nts long depending on the species. The 5’ end of U7 snRNA binds to a sequence 3’ of the stemloop, termed the histone downstream element (HDE). There are a number of proteins found in the U7 snRNP. There are 7 Sm proteins, as are present in the spliceosomal snRNP. Five of these proteins are the same as ones found in the spliceosomal snRNPs and there are 2, Lsm10 and Lsm11 that are unique to U7 snRNP.
R-HSA-77584 (Reactome) The 32 kDa stem-loop binding protein (SLBP), also termed hairpin binding protein (HBP) is likely the first protein that binds to the histone pre-mRNA as it is being transcribed.
R-HSA-77585 (Reactome) The U7 snRNP. This particle contains the U7 snRNA, the smallest of the snRNAs which varies from 57-70 nts long depending on the species. The 5’ end of U7 snRNA binds to a sequence 3’ of the stemloop, termed the histone downstream element (HDE). There are a number of proteins found in the U7 snRNP. There are 7 Sm proteins, as are present in the spliceosomal snRNP. Five of these proteins are the same as ones found in the spliceosomal snRNPs and there are 2, Lsm10 and Lsm11 that are unique to U7 snRNP. A third protein joins the U7 snRNP, ZFP100, a large zinc finger protein. ZFP100 interacts with SLBP bound to the histone pre-mRNA and with Lsm11 and likely plays a critical role in recruiting U7 snRNP to the histone pre-mRNA.
R-HSA-77586 (Reactome) Processing is initiated once the SLBP (bound to the stem loop) and the U7 snRNP (bound to the HDE) are both loaded onto the pre-mRNA. The pre-mRNA HDE makes base-pairing contacts with the 5�² end of U7 snRNA. Binding of the U7 snRNP to the pre-mRNA is stabilized by interactions between a U7 snRNP protein, hZFP100 and SLBP. It should be noted that there must be other trans-acting factors, including the factor that catalyzes the cleavage reaction, which have yet to be defined. The cleavage occurs in the presence of EDTA as does the cleavage reaction in polyadenylation, it is likely that this reaction is catalyzed by a protein. There may well be additional proteins associated with the U7 snRNP, and since in some conditions in vitro processing occurs in the absence of SLBP, it is possible that all the other factors required for processing are associated with the active form of the U7 snRNP.
R-HSA-77589 (Reactome) Poly(A) polymerase has no specificity for any particular RNA sequence, as well as a very low affinity for the RNA. Under physiological conditions, the activity of poly(A) polymerase depends on two auxiliary factors, both of which bind to specific RNA sequences and recruit the poly(A) polymerase by a direct contact. One of these proteins is the heterotetrameric CPSF, which binds the AAUAAA sequence and is also essential for 3' cleavage.
R-HSA-77590 (Reactome) Endonucleolytic cleavage separates the pre-mRNA into an upstream fragment destined to become the mature mRNA and a downstream fragment that is rapidly degraded. Polyadenylation and cleavage occur concurrently, with complexes co-assembling, cleavage depends on two signals in the RNA, a highly conserved hexanucleotide, AAUAAA, 10 to 30 nucleotides upstream of the cleavage site, and a poorly conserved GU- or U-rich downstream element. Additional sequences, often upstream of AAUAAA, can enhance the efficiency of the reaction. Cleavage occurs most often after a CA dinucleotide. A single gene can have more than one 3' processing site.

Cleavage is preceded by the assembly of a large processing complex, the composition of which is poorly defined. ATP, but not its hydrolysis, is required for assembly. Cleavage depends on a number of protein factor. CPSF, a heterotetramer, binds specifically to the AAUAAA sequence. The heterotrimer CstF binds the GU- or U-rich downstream element.

R-HSA-77591 (Reactome) CF I, which appears to be composed of two subunits, one of several related larger polypeptides and a common smaller one, also binds RNA, but with unknown specificity. RNA recognition by these proteins is cooperative. Cleavage also requires CF II, composed of at least two subunits, and poly(A) polymerase, the enzyme synthesizing the poly(A) tail in the second step of the reaction.
R-HSA-77592 (Reactome) The polypeptide catalyzing the hydrolysis of the phosphodiester bond remains to be identified. Cleavage produces a 3'-OH on the upstream fragment and a 5'-phosphate on the downstream fragment. At some unknown point after cleavage, the downstream fragment, CstF, CF I and CF II are thought to be released, whereas CPSF and poly(A) polymerase remain to carry out polyadenylation.
R-HSA-77593 (Reactome) The nuclear poly(A) binding protein (PABPN1), which binds the growing poly(A) tails once it has reached a length of about ten nucleotides. Stimulation of poly(A) polymerase by both CPSF and PABPN1 is synergistic and results in processive elongation of the RNA (the polymerase adds AMP residues without dissociating from the RNA). The processive reaction is terminated when the tail has reached a length of about 250 nucleotides.
SLBPR-HSA-77584 (Reactome)
U7 snRNP:ZNF473ArrowR-HSA-111437 (Reactome)
U7 snRNP:ZNF473ArrowR-HSA-77586 (Reactome)
U7 snRNP:ZNF473R-HSA-111438 (Reactome)
U7 snRNP:ZNF473R-HSA-77585 (Reactome)
capped intronless

pre-mRNA:CBC

complex
R-HSA-77589 (Reactome)
downstream

intronless mRNA

fragment
ArrowR-HSA-77592 (Reactome)
intronless pre-mRNA cleavage complexArrowR-HSA-77591 (Reactome)
intronless pre-mRNA cleavage complexR-HSA-77592 (Reactome)
intronless pre-mRNA cleavage complexR-HSA-77593 (Reactome)
upstream

mRNA

fragment:CPSF:PAP:PABPN1 complex
ArrowR-HSA-77592 (Reactome)

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